Semaglutide

Overall Health Benefits of Semaglutide

• Promotes fat loss [1-41]
• Fights type 2 diabetes [42-69]
• Prevents cognitive decline [70-81]
• Lowers blood pressure [4] [82-88]
• Lowers the risk of cardiovascular disease [89-96]

What is Semaglutide?

Semaglutide is an injectable FDA-approved medication for type 2 diabetes that is known to possess fat-burning properties. It belongs to a class of medications known as glucagon-like peptide-1 receptor agonists (GLP-1 RA). At higher doses, semaglutide promotes fat loss by suppressing your appetite. When combined with lifestyle modifications such as proper diet and exercise, semaglutide produces amazing results.

How Semaglutide Works

As a glucagon-like peptide-1 receptor agonist (GLP-1 RA), it increases the secretion of the hormone insulin which helps the cells to effectively utilize energy. This process ensures proper fat storage and decreases blood sugar levels. Semaglutide also suppresses your appetite and slows gastric emptying by blocking certain chemicals in the brain. This in turn helps promote fat loss.

Chemical Structure of Semaglutide

Research on Semaglutide

A. Promotes Fat Loss

Semaglutide can help promote weight loss by reducing the drive to eat and inhibiting food intake. [1] It appears that this GLP-1 RA may actually promote fat loss and help achieve a healthy weight by enhancing feelings of satiety.

Semaglutide’s fat-burning properties are backed by a number of high-quality studies:

1. In overweight and obese participants, semaglutide administration once a week resulted in relevant reduction in body weight. [2]
2. In obese people, administration of semaglutide once a week via subcutaneous injects produced superior weight loss compared to placebo. [3]
3. In obese patients with type 2 diabetes, administration of semaglutide demonstrated huge weight loss efficacy. [4]
4. In overweight and obese adults, treatment with 2.4 mg semaglutide once weekly resulted in continued weight loss for the following 48 weeks. [5]
5. A study showed that combination of physical activity and dietary supplementation of semaglutide resulted in greater weight loss. [6]
6. In obese, overweight, and type-2 diabetic adults, administration of 2.4 mg semaglutide once a week decreased bodyweight. [7]
7. Among overweight and obese patients, Semaglutide used as an intensive behavioral therapy and initial low-calorie diet result to greater weight loss during 68 weeks. [8]
8. A study showed that semaglutide induced weight loss in subjects with type 2 diabetes regardless of baseline body mass index (BMI). [9]
9. In obese adults, administration of semaglutide 2.4 mg once a week suppressed appetite, improved control of eating, and reduced food cravings, compared to placebo. [10]
10. In obese subjects, semaglutide administration once a week reduced appetite and food cravings, and was associated with better control of eating and lower relative preference for fatty, energy‐dense foods. [11]
11. A study showed that semaglutide administration once a day produced weight loss by reducing HbA1c, a measure of blood sugar. [12]
12. A study showed that intake of semaglutide once a week improved blood sugar control and reduced body weight in patients with type-2 diabetes. [13]
13. Studies showed that semaglutide lowers body weight by directly and indirectly affecting the activity of neural pathways involved in food intake, reward, and energy expenditure, without any adverse side effects. [14-16]
14. Studies suggest that semaglutide is superior to other weight loss medications with regards to efficacy and cost-effectiveness. [17-25]
15. In overweight and obese adults, once per week administration of semaglutide resulted in significant and sustained weight reduction. [26]
16. In obese patients, semaglutide was well-tolerated and induced significant weight loss. [27]
17. A review of studies showed that once weekly semaglutide was successful in inducing significant weight loss. [28]
18. A study showed that oral semaglutide was effective in body weight reduction. [29]
19. A review of studies showed that semaglutide demonstrated superior efficacy in obesity compared to other anti-diabetic drugs. [30]
20. In obese or overweight adults, semaglutide administration resulted in significant weight loss. [31]
21. In obese or overweight adults, semaglutide administration in addition to weight management program was effective in inducing weight reduction. [32]
22. A study showed that semaglutide offered the greatest weight-reducing effect among any obesity medication. [33]
23. In obese or overweight adults, once-weekly administration of semaglutide resulted in significant weight loss. [34]
24. In adults with overweight or obesity, weekly treatment with subcutaneous semaglutide at a dose of 2.4 mg for 20 weeks resulted in continued weight loss over the following 48 weeks compared with placebo. [35]
25. In adults with obesity, with or without type 2 diabetes, the administration of semaglutide at a dose of 2.4 mg once a week for 68 weeks resulted in superior and clinically meaningful reductions in bodyweight and abdominal visceral fat area compared with placebo. [36-39]
26. Once-weekly administration of subcutaneous semaglutide as an adjunct to intensive behavioral therapy and initial low-calorie diet in adults with overweight or obesity produced significant weight loss after 68 weeks. [40]
27. In patients with a body mass index (BMI) of 27 or more, weekly 1.7-mg and 2.4-mg doses of semaglutide resulted in a mean weight loss of 6.7 kg at 3 months and 12.3 kg at 6 months. [41]

B. Fights Type 2 Diabetes

Semaglutide may help bring blood sugar to normal levels through the incretin effect. [42] Incretins such as semaglutide and other GLP-1 RA cause a decrease in blood sugar levels once released by the gastrointestinal tract. This in turn alleviates symptoms of diabetes and keeps blood sugar within normal limits.

Studies show that semaglutide, an FDA-approved medication for diabetes, has potent blood-sugar lowering effects:

1. In patients with type 2 diabetes, semaglutide administration once a week resulted in decreased blood sugar levels. [43]
2. A study showed that oral administration of semaglutide in type 2 diabetics reduced glycosylated hemoglobin, which is chemically linked to sugar. [44]
3. In patients with type 2 diabetes, oral semaglutide improved blood sugar control. [45]
4. A study showed that oral semaglutide can effectively and safely reduce blood sugar, body weight and systolic blood pressure. [46]
5. In adults with type 2 diabetes clinical trials showed the efficacy of semaglutide in reducing blood sugar levels. [47]
6. In adult type 2 diabetic patients, once per week therapy with semaglutide resulted in significant reductions in blood sugar levels and body weight after 3 to 6 months. [48]
7. A review of studies showed that oral semaglutide administration is effective in treating type 2 diabetes without increasing the incidence of major adverse effects. [49]
8. In Japanese patients with type 2 diabetes, semaglutide was efficacious in reducing blood sugar levels and was well-tolerated. [50]
9. In type 2 diabetic patients, semaglutide was shown to be highly effective in controlling blood sugar levels compared with other diabetic medications. [51-66]
10. In patients with type 2 diabetes, semaglutide administration at a dose of 2.0 mg was superior to 1.0 mg in reducing HbA1c (a measure of blood sugar in the past 3 months), with additional bodyweight loss and a similar safety profile. [67-68]
11. Once-daily oral semaglutide (4-week dose escalation from 3 to 7 to 14 mg) administration in type 2 diabetics resulted in reduced body fat mass, increased satiety and fullness after a fat-rich breakfast, and improved eating control compared with placebo. [69]

C. Prevents Cognitive Decline

Semaglutide can help protect brain cells against injury or damage through its anti-inflammatory and antioxidant properties. By reducing inflammation and oxidative stress (free radicals), semaglutide can help improve cognitive function.

Evidence shows that semaglutide has the capacity to prevent age-related cognitive decline and cognitive dysfunction due to brain disorders:

1. In mice models of Parkinson’s disease (PD), semaglutide produced significant neuroprotective and cognitive-enhancing effects. [70]
2. In PD mouse models, semaglutide attenuated the effects of the disease by protecting the brain neurons against injury. [71]
3. In animal models, semaglutide protected against diabetes and obesity-related cognitive deficits. [72]
4. In a mouse model of PD, semaglutide exerted its neuroprotective effects by reducing motor impairments. [73]
5. Studies in rodent models of Parkinson’s and Alzheimer’s diseases and mouse models of ischemic stroke have shown that semaglutide prevented brain neuron damage and memory impairment. [74-77]
6. In non-diabetic rat model of acute ischemic stroke, semaglutide reduced infarct size (dead brain tissue) by up to 90%. [78]
7. In a Parkinson’s disease mouse model, semaglutide alleviated the inflammation response, reduced lipid peroxidation (oxidative stress), and inhibited programmed cell death. [79-81]

D. Lowers Blood Pressure

Stimulation of the glucagon-like peptide-1 receptor is known to increase blood pressure. [82] As a glucagon-like peptide-1 receptor agonist, semaglutide suppresses the release of glucagon by the liver which in turn lowers blood pressure.

The blood pressure-lowering effects of semaglutide are backed by a number of studies:

1. In overweight and obese adults, subcutaneous injection of semaglutide reduced systolic blood pressure after 20 weeks. [4]
2. A review of multiple studies found that semaglutide lowered blood pressure compared to placebo. [83]
3. In patients with type 2 diabetes, oral semaglutide effectively and safely reduced systolic blood pressure. [84]
4. Studies found that glucagon-like peptide-1 receptor agonists such as semaglutide can significantly reduce elevated blood pressure with a low risk of adverse effects. [85-86]
5. A study found that both doses of semaglutide (0.5 and 1.0 mg) were associated with reductions in systolic blood pressure. [87-88]

E. Lowers the Risk of Cardiovascular Disease

Evidence shows that semaglutide can help lower the risk of heart disease possibly through its beneficial effects on obesity, blood sugar, and blood pressure:

1. In patients with type 2 diabetes, oral semaglutide reduced the rate of cardiovascular death and nonfatal myocardial infarction. [89]
2. In subjects with type 2 diabetes and high cardiovascular disease risk, semaglutide (0.5 and 1.0 mg) administration once a week significantly reduced major adverse cardiovascular events. [90-91]
3. In patients with type 2 diabetes who are at high risk for cardiovascular disease, the addition of semaglutide to standard treatment decreased cardiovascular risk by reducing blood sugar and body weight. [92]
4. Studies found that semaglutide decreased the risk of atherosclerosis (plaque formation within the heart arteries) and other cardiovascular events in diabetic patients. [93-96]

Associated Side Effects of Semaglutide

Semaglutide side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on semaglutide. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of semaglutide. Despite this, it was listed as a side effect associated with semaglutide even these associated side effects are very uncommon.

Side effects associated with semaglutide may include the following:

• Abdominal pain
• Constipation
• Diarrhea
• Loss of appetite
• Nausea
• Vomiting

Semaglutide vs Liraglutide

An overwhelming body of clinical evidence shows that semaglutide is superior to liraglutide (weight loss medication) in reducing body weight and blood sugar levels:

1. In patients with obesity but without type 2 diabetes, semaglutide subcutaneous injection once daily demonstrated superior weight loss efficacy compared with both placebo and once daily 3.0 mg liraglutide. [5]
2. In obese patients, semaglutide injection in combination with dietary and physical activity counselling produced clinically relevant weight loss over 52 weeks compared with liraglutide at all doses. [7]
3. In adults with type 2 diabetes, subcutaneous semaglutide 1 mg once per week was superior to liraglutide in reducing HbA1c (a measure of blood sugar) and body weight. [8]
4. In subjects with inadequately controlled type 2 diabetes, semaglutide-induced weight loss was consistently greater than liraglutide, regardless of baseline BMI. [10]
5. A study reported that semaglutide demonstrated superior HbA1c and body weight reductions compared with liraglutide 1.2 mg. [16]
6. In diabetic patients who were aged 18 years or older, once-daily oral semaglutide (dose escalated to 14 mg) for 52 weeks was superior to once-daily subcutaneous liraglutide and placebo in reducing blood sugar levels and body weight. [52]
7. A study reported that up to 81% of patients achieved reductions in weight and HbA1c with semaglutide 1.6 mg for 12 weeks than those with liraglutide 1.2 and 1.8 mg. [54]
8. Several studies showed that both oral and injectable semaglutide demonstrated greater efficacy than liraglutide in reducing body weight and blood sugar levels. [55-66]
9. The global SUSTAIN and PIONEER phase III clinical trial programs found that subcutaneous semaglutide 1 mg once a week reduced HbA1c by 1.5-1.8% after 30-56 weeks, which was significantly more than liraglutide. [97]

References:

1. Drucker D. J. (2018). Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell metabolism, 27(4), 740–756. https://doi.org/10.1016/j.cmet.2018.03.001.
   View Summary +

   Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1

   By raising insulin production and reducing glucagon secretion, the hormone glucagon-like peptide-1 (GLP-1) regulates blood sugar levels before and after meals. It is secreted from the gut’s endocrine cells. Additionally, it slows down the emptying of the stomach and reduces appetite, allowing for more effective nutrition absorption. This process also helps with weight gain.

   A review focused on the mechanisms involved in the actions of natural and synthetic GLP-1, highlighting the cell types that express the GLP-1 receptor (GLP-1 R) and the signaling pathways that mediate the hormone’s metabolic and non-glycemic effects. The review also discussed the role of GLP-1 in the context of bariatric surgery, as well as its impact on inflammation, cardiovascular health, appetite control, and pancreatic function. The discovery of novel GLP-1 R agonists, which include orally bioavailable agonists, allosteric modulators, and multi-agonists, is noted in this review. It was found that in the first 10 years of GLP-1 therapeutics, the use of these medications in patients with type 2 diabetes mellitus and obesity is growing. In contrast to insulin, GLP-1 R agonists were associated with a lower risk of cardiovascular events such as myocardial infarction, cardiovascular death, and stroke.

   The development of next-generation improved GLP-1 therapies need a thorough understanding of their mechanisms of action. Advances in understanding how certain factors such as bacteria, microbes, and nutrients control enteroendocrine cells (EECs) GLP-1 secretion may provide an opportunity for the development of more potent GLP-1 secretagogues.

2. Wilding, J., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., Kushner, R. F., & STEP 1 Study Group (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England journal of medicine, 384(11), 989. https://doi.org/10.1056/NEJMoa2032183.
   View Summary +

   Once-Weekly Semaglutide in Adults with Overweight or Obesity

   With few medicinal solutions available, obesity is a severe global health issue. This condition can lead to health problems such as insulin resistance, hypertension, and dyslipidemia (abnormal lipid levels). More recently, obesity has been linked to a significant increase in the rate of hospitalizations and deaths. Although lifestyle intervention that includes proper diet and exercise remains the cornerstone of managing obesity, achieving long-term weight loss poses a significant challenge.

   A study determined whether once-weekly administration of semaglutide at a dose of 2.4 mg along with a lifestyle intervention may help adults with obesity lose weight. A total of 1961 adults with a body-mass index (BMI) of 30 or above (or ≥27 in individuals with at least one weight-related medical condition) and without diabetes were enrolled in the study. Participants were randomly assigned to receive either a once-weekly subcutaneous semaglutide or a placebo for 68 weeks in combination with lifestyle intervention. The coprimary endpoints were the percentage change in body weight and weight reduction of at least 5%.

   Results showed that participants who received semaglutide experienced greater improvements in cardiometabolic risk factors and physical functioning than those who received a placebo. Although nausea and diarrhea were the most frequent side effects associated with semaglutide, they were often mild to moderate in intensity and eventually went away. In comparison to the placebo group, more participants in the semaglutide group stopped taking the medication due to gastrointestinal problems.

   In conclusion, the study found that semaglutide, in combination with lifestyle intervention, was associated with a sustained and clinically relevant reduction in body weight in individuals with overweight or obesity.

3. Kushner, R. F., Calanna, S., Davies, M., Dicker, D., Garvey, W. T., Goldman, B., Lingvay, I., Thomsen, M., Wadden, T. A., Wharton, S., Wilding, J., &Rubino, D. (2020). Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring, Md.), 28(6), 1050–1061. https://doi.org/10.1002/oby.22794.
   View Summary +

   Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5

   Public health officials are becoming increasingly concerned about the obesity pandemic. To manage this situation, more research into pharmacological approaches to supporting weight management in conjunction with lifestyle changes is required.

   In order to find out how semaglutide compares to placebo in terms of weight loss, safety, and tolerability in individuals who are overweight or obese, the Semaglutide Treatment Effect in People with Obesity (STEP) program has been established. The STEP program encompasses five phase 3 trials that focus on the different aspects of weight management, including weight management in type 2 diabetes, weight management with intensive behavioral therapy, sustained weight management, and long-term weight management. Roughly 5,000 participants are being randomly assigned to receive a once-weekly subcutaneous injection of semaglutide 2.4 mg or a placebo. The participants range in age from 46.2 to 55.3 years, are mostly female, and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm.

   In a broad population, the STEP program aims to evaluate the efficacy and safety of semaglutide 2.4 mg once weekly administered subcutaneously. The trials could lead to new and more effective ways to address the obesity epidemic by shedding light on the possible advantages and disadvantages of this weight-management therapy option. As a researcher, it is critical to keep looking into and assessing fresh approaches to help people who are obese or overweight healthily maintain their weight.

4. Christou, G. A., Katsiki, N., Blundell, J., Fruhbeck, G., &Kiortsis, D. N. (2019). Semaglutide as a promising antiobesity drug. Obesity reviews : an official journal of the International Association for the Study of Obesity, 20(6), 805–815. https://doi.org/10.1111/obr.12839.
   View Summary +

   Semaglutide as a promising antiobesity drug

   An agonist for the glucagon-like peptide-1 receptor (GLP-1 RA), semaglutide is a medication that can be administered subcutaneously once every week. Recently, once-weekly subcutaneous semaglutide for the treatment of type 2 diabetes mellitus (T2DM) received approval from both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

   Researchers have shown that once-weekly subcutaneous semaglutide appears to be more effective than other once-weekly GLP-1 RAs in patients with T2DM for weight loss. In a phase II dose-finding trial, semaglutide was evaluated as an anti-obesity medication, demonstrating superior weight loss efficacy when administered once daily subcutaneously compared to both placebo and once-daily 3.0 mg liraglutide in patients with obesity but without T2DM. The degree of semaglutide-induced weight loss in this study exceeded the EMA and FDA’s criteria for anti-obesity drugs and there were no safety concerns, indicating the potential of once-daily subcutaneous semaglutide as an anti-obesity drug in the future.

5. Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., Dicker, D., & STEP 4 Investigators (2021). Effect of Continued Weekly Subcutaneous Semaglutidevs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA, 325(14), 1414–1425. https://doi.org/10.1001/jama.2021.3224.
   View Summary +

   Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity

   The study’s goal was to evaluate the effectiveness of continuing treatment with subcutaneous semaglutide 2.4 mg versus switching to a placebo for people who had completed a 20-week run-in phase with the drug. A total of 902 patients received once-weekly subcutaneous semaglutide during the run-in phase of the research. Out of these, 803 participants who reached the semaglutide maintenance dose were randomized to 48 weeks of continued subcutaneous semaglutide or switched to placebo, both with lifestyle intervention.

   The researchers found that among adults who were overweight or obese who completed the 20-week run-in period with subcutaneous semaglutide, maintaining treatment with semaglutide resulted in continued weight loss over the following 48 weeks compared to switching to placebo. The study emphasized the significance of continuing subcutaneous semaglutide therapy for weight loss in people who are overweight or obese. The findings of the study revealed that semaglutide-treated participants continued to lose weight whereas those who switched to placebo did not see any discernible weight loss. Waist circumference, systolic blood pressure, and physical functioning score also improved in participants who continuously used semaglutide than in the placebo-treated group. The need for lifestyle changes in addition to medicine is also emphasized in the study as a key component of effective weight management.

   In conclusion, the study suggests that continued treatment with subcutaneous semaglutide 2.4 mg along with lifestyle intervention is effective for weight maintenance in adults who are overweight or obese. The researchers recommend the use of subcutaneous semaglutide as a part of a comprehensive weight loss management program for individuals who are overweight or obese.

6. O’Neil, P. M., Birkenfeld, A. L., McGowan, B., Mosenzon, O., Pedersen, S. D., Wharton, S., Carson, C. G., Jepsen, C. H., Kabisch, M., & Wilding, J. (2018). Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet (London, England), 392(10148), 637–649. https://doi.org/10.1016/S0140-6736(18)31773-2.
   View Summary +

   Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial

   Obesity is a major public health issue worldwide. In this case, new medications to address this condition are needed. Therefore, a study evaluated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in comparison with another GLP-1 analogue liraglutide and placebo in promoting weight loss.

   The study, a phase 2 multicenter, dose-ranging trial including 71 clinical sites across eight nations, was conducted. Adults without diabetes and those with a BMI of 30 kg/m2 or higher qualified as participants. The participants were randomly assigned to each active treatment group, semaglutide, liraglutide, or a corresponding placebo group using a block size of 56 in the study’s randomized, double-blind, placebo-controlled design. Subcutaneous injections were used to administer all therapy doses once a day. The primary endpoint of the study was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. The researchers found that all semaglutide doses were generally well tolerated with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, which were previously seen with GLP-1 receptor agonists.

   The researchers concluded that semaglutide was well tolerated over 52 weeks when used in conjunction with dietary and exercise counseling and demonstrated clinically meaningful weight loss as compared to placebo at all doses. Semaglutide may be a useful new pharmacological alternative for weight management, addressing the public health problem of obesity, according to the study’s findings.

7. Davies, M., Færch, L., Jeppesen, O. K., Pakseresht, A., Pedersen, S. D., Perreault, L., Rosenstock, J., Shimomura, I., Viljoen, A., Wadden, T. A., Lingvay, I., & STEP 2 Study Group (2021). Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet (London, England), 397(10278), 971–984. https://doi.org/10.1016/S0140-6736(21)00213-0.
   View Summary +

   Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

   A group of researchers conducted a phase 3 clinical trial to examine the efficacy and safety of subcutaneous semaglutide 2.4 mg once per week, semaglutide 1.0 mg (licensed for the treatment of diabetes), and placebo in managing weight in an adult population who were overweight or obese and have type 2 diabetes. Adults with a body mass index of at least 27 kg/m2 and glycated hemoglobin levels between 7 and 10% who had been diagnosed with type 2 diabetes for at least 180 days prior to screening were included in the double-blind, double-dummy study.

   In 149 outpatient clinics spread across 12 nations in Europe, North America, South America, the Middle East, South Africa, and Asia, the trial was carried out. Patients were randomly allocated to receive subcutaneous injections of semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo once a week for 68 weeks, along with lifestyle intervention. The coprimary endpoints of the trial were the percentage change in body weight and achieving a weight reduction of at least 5% at 68 weeks for semaglutide 2.4 mg versus placebo, assessed by intention to treat. Safety was assessed in all patients who received at least one dose of the study drug.

   According to the trial’s findings, semaglutide 2.4 mg once a week was considerably more effective than a placebo at helping adults with type 2 diabetes who were overweight or obese lose body weight. The decrease in body weight was regarded as clinically significant. Semaglutide 2.4 mg had a similar safety profile to semaglutide 1.0 mg and placebo. At week 68, patients who received semaglutide achieved weight reductions of at least 5% compared to the placebo-treated group. In addition, mild to moderate gastrointestinal side effects were more frequent in the semaglutide-treated group compared to the placebo-treated group.

   In conclusion, the study demonstrated that semaglutide 2.4 mg once a week, in combination with lifestyle intervention, can effectively manage weight in adults with obesity and type 2 diabetes. The findings have important clinical implications and suggest that semaglutide 2.4 mg could be an effective option for managing weight in this patient population.

8. Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O’Neil, P. M., Rubino, D. M., Skovgaard, D., Wallenstein, S., Garvey, W. T., & STEP 3 Investigators (2021). Effect of Subcutaneous Semaglutidevs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA, 325(14), 1403–1413. https://doi.org/10.1001/jama.2021.1831.
   View Summary +

   Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial

   Among people who are overweight or obese, it is well established that weight loss can reduce cardiometabolic risk factors. Pharmacotherapy and rigorous lifestyle modification are the two most efficient noninvasive methods for weight loss.

   A randomized controlled trial was carried out to examine the effectiveness of once-weekly subcutaneous semaglutide 2.4 mg as an addition to intensive behavioral therapy and initial low-calorie diet in individuals with overweight or obesity. The goal was to compare semaglutide’s weight-loss results over 68 weeks with those of a placebo. Participants were randomized to receive either semaglutide or placebo in a 2:1 ratio, combined with a low-calorie diet for the first 8 weeks, followed by intensive behavioral therapy for 68 weeks, including 30 counseling visits. The study found that adults with overweight or obesity who received semaglutide, compared to those who received placebo, experienced a significant reduction in weight over the 68-week period. According to the findings of the study, a once-weekly subcutaneous semaglutide regimen combined with intense behavioral treatment and an initial low-calorie diet can help people who are overweight or obese lose weight. To ascertain whether these findings will be valid in the long run, more study is required.

   In conclusion, the researchers found that semaglutide is a promising weight loss treatment option for individuals with overweight or obesity. When combined with intensive behavioral therapy and a low-calorie diet, it can result in greater weight loss. These findings have important implications for the management of overweight and obesity, as well as the prevention of associated cardiometabolic risk factors. However, additional research is needed to determine the long-term effects and durability of this treatment approach.

9. Ahrén, B., Atkin, S. L., Charpentier, G., Warren, M. L., Wilding, J., Birch, S., Holst, A. G., &Leiter, L. A. (2018). Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes, obesity & metabolism, 20(9), 2210–2219. https://doi.org/10.1111/dom.13353.
   View Summary +

   Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials

   In the SUSTAIN 1 to 5 studies, semaglutide was found to cause more weight loss and HbA1c level reductions than other drugs, although the underlying mechanisms causing this weight loss were not previously known. To determine the weight loss effects of semaglutide, a once-weekly glucagon-like peptide 1 analogue used to treat type 2 diabetes, a group of researchers included subjects with poorly controlled type 2 diabetes who were either drug-naïve or on background treatment in a study.

   The subjects were randomly assigned to receive subcutaneous semaglutide at doses of 0.5 mg or comparator medications (placebo, sitagliptin, exenatide extended-release, or insulin glargine). The subjects were categorized based on their baseline BMI and whether they experienced nausea and/or vomiting. The researchers assessed the change in body weight from baseline within each trial and subgroup and they also carried out a mediation analysis to differentiate between direct and indirect effects of semaglutide on weight loss, the latter of which was mediated by nausea or vomiting. The results of the study showed that semaglutide consistently induced greater weight loss compared to comparators across all trials, irrespective of baseline BMI. The role of nausea or vomiting in this weight loss was found to be minor, indicating that the weight loss effects of semaglutide were primarily due to direct mechanisms unrelated to nausea or vomiting.

   In conclusion, the researchers found that semaglutide was effective in promoting weight loss in subjects with poorly controlled type 2 diabetes, regardless of their baseline BMI. While nausea and vomiting were observed in some subjects, these symptoms were not significant mediators of the weight loss effects of semaglutide.

10. Friedrichsen, M., Breitschaft, A., Tadayon, S., Wizert, A., &Skovgaard, D. (2021). The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating,and gastric emptying in adults with obesity. Diabetes, obesity & metabolism, 23(3), 754–762. https://doi.org/10.1111/dom.14280.
    View Summary +

    The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity

    A study investigated the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in people with obesity. In a double-blind, parallel-group trial, the researchers randomly assigned 72 obese people to receive semaglutide or placebo.

    For 20 weeks, the subjects were given semaglutide (dose-escalated to 2.4 mg) or a placebo. To measure stomach emptying after a typical breakfast, the researchers utilized paracetamol absorption. They examined caloric intake during an open-ended meal as well as participant-reported appetite ratings and Control of Eating Questionnaire (CoEQ) responses. The results of the study showed that once-weekly s.c. semaglutide 2.4 mg had a significant impact on the appetite and eating habits of adults with obesity. The researchers found that the medication suppressed appetite, improved control of eating, and reduced food cravings, ad libitum energy intake, and body weight compared to the placebo. Interestingly, there was no evidence of delayed gastric emptying at week 20, assessed indirectly via paracetamol absorption. The study concluded that once-weekly s.c. semaglutide 2.4 mg may be a useful therapy choice for obese people who have trouble controlling their appetites and eating patterns. Food cravings appeared to be significantly reduced by semaglutide, which may make it easier for people to stick to healthier eating habits and lose weight. Additionally, the absence of evidence of delayed stomach emptying shows that the drug has no negative effects on the digestive system, which is crucial to take into account when assessing the efficacy and safety of weight-loss drugs.

    Overall, the study provides valuable insights into the potential benefits of once-weekly s.c. semaglutide 2.4 mg as a treatment option for adults with obesity. The findings highlight the importance of addressing appetite control and eating habits in the management of obesity and suggest that medications like s.c. semaglutide may be a useful tool in this regard. Further research is needed to fully understand the long-term effects and safety profile of this medication but the results of this study provide a promising foundation for future investigations.

11. Blundell, J., Finlayson, G., Axelsen, M., Flint, A., Gibbons, C., Kvist, T., &Hjerpsted, J. B. (2017). Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes, obesity & metabolism, 19(9), 1242–1251. https://doi.org/10.1111/dom.12932.
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    Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity

    The goal of the study was to find out how semaglutide encourages weight loss. The researchers included 30 obese patients in a randomized, double-blind, placebo-controlled, two-period crossover experiment over a 12-week period to accomplish this. Semaglutide was administered subcutaneously to the subjects once per week at doses that were eventually increased to 1.0 mg.

    Throughout the trial, the researchers measured several variables related to appetite, eating behavior, and metabolism. These included ad libitum energy intake, ratings of appetite, thirst, nausea, well-being, control of eating, food preference, resting metabolic rate, body weight, and body composition. The results of the trial showed that semaglutide was associated with less hunger and food cravings, better control of eating, and a lower preference for high-fat foods. However, resting metabolic rate, adjusted for lean body mass, did not differ between treatments. The study’s most important finding was the average 5.0 kg drop in body weight that was seen with semaglutide, mostly due to a reduction in body fat mass. This weight loss was probably caused by a decrease in energy intake but the researchers also discovered a number of additional processes that may have helped, such as a decrease in hunger and food cravings, improved behavior control for eating, and a decreased relative preference for fatty, energy-dense foods.

    Overall, the study provided important insights into the mechanism of action for semaglutide-induced weight loss. The findings suggest that semaglutide may be a useful tool in the management of obesity, not only due to its effects on energy intake but also due to its impact on appetite and eating behavior.

12. Available from https://care.diabetesjournals.org/content/41/9/1926.figures-only.
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    A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin

    Glucagon-like peptide 1 (GLP-1) is a powerful hormone that significantly decreases blood glucose (sugar) levels. GLP-1 is derived from the gut and lowers the risk of hypoglycemia (low blood sugar levels). GLP-1 also decreases body weight and calorie consumption by preventing stomach emptying and producing feelings of fullness.

    The hypothalamus, a part of the brain that controls satiety and appetite, is considered to express GLP-1 receptors, which are thought to play a role in weight loss. These characteristics have made GLP-1 medicines a crucial part of managing type 2 diabetes, along with indications that some GLP-1 receptor agonists can enhance cardiovascular outcomes.

    A 26-week, multicenter, double-blind trial assessed the efficacy and safety of once-daily semaglutide compared to once-daily liraglutide and placebo in patients with type 2 diabetes. The study included patients with HbA1c levels ranging from 7.0-10.0% (53-86 mmol/mol) who were being treated with diet and exercise with or without metformin. The researchers randomized the patients into three groups: once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). The HbA1c change between baseline and week 26 was the main goal. The findings demonstrated that when compared to liraglutide or placebo, once-daily semaglutide at doses up to 0.3 mg/day caused larger reductions in HbA1c. Patients who received semaglutide, however, reported more gastrointestinal adverse events (AEs).

    The study’s findings show that semaglutide may be a better treatment option for lowering HbA1c levels in type 2 diabetic patients than liraglutide or a placebo. However, when selecting a course of treatment, it is important to take into account the frequency of gastrointestinal adverse events (AEs).

13. Ji, L., Dong, X., Li, Y., Li, Y., Lim, S., Liu, M., Ning, Z., Rasmussen, S., Skjøth, T. V., Yuan, G., &Eliaschewitz, F. G. (2021). Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30-week, double-blind, phase 3a, randomized trial. Diabetes, obesity & metabolism, 23(2), 404–414. https://doi.org/10.1111/dom.14232.
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    Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30-week, double-blind, phase 3a, randomized trial

    Due to increased obesity and inactivity rates, type 2 diabetes (T2D) is a complex, multifaceted disease with a rising prevalence rate. T2D was present in 116.4 million people (10.9%) in China in 2019 and it is predicted that this figure will rise to 140.5 million by 2030, placing a considerable load on the country’s healthcare system.

    Optimizing glycemic control to reduce the risks of microvascular and macrovascular consequences is the main goal of T2D care. Semaglutide is a long-acting GLP-1 RA medication that is administered once weekly and is authorized for the treatment of T2D under the brand name Ozempic®. The GLP-1 portion of semaglutide has been modified by adding a fatty diacid chain and making two amino acid substitutions. These modifications enhance its half-life by increasing albumin binding and inhibiting degradation by DPP-4, allowing for once-weekly dosing. The efficacy and safety of semaglutide have been established in over 10,000 patients in the SUSTAIN clinical trial program.

    In a multiregional clinical trial, researchers compared the safety and efficacy of once-weekly subcutaneous injections of semaglutide, an analog of glucagon-like peptide-1 (GLP-1), to once-daily injections of sitagliptin in patients with type 2 diabetes (T2D). Semaglutide has consistently demonstrated better reductions in HbA1c and body weight compared to placebo and a variety of active comparators, including sitagliptin, exenatide extended release, insulin glargine, dulaglutide, canagliflozin, and liraglutide. In addition, semaglutide was associated with a significant 26% reduction in major adverse cardiovascular events compared to placebo in a preapproval cardiovascular outcomes trial (CVOT).

    In conclusion, the researchers discovered that once-weekly semaglutide was more effective than sitagliptin in improving glycemic control and reducing body weight in T2D patients who were inadequately controlled on metformin. The safety and tolerability profiles of semaglutide were comparable to those of other GLP-1 RAs. Semaglutide is an efficient once-weekly treatment alternative for the Chinese population with T2D.

14. Available from https://insight.jci.org/articles/view/133429.
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    Semaglutide lowers body weight in rodents via distributed neural pathways

    Six GLP-1 receptor agonists, including four long-acting drugs, have been discovered to be approved for the treatment of type 2 diabetes, according to research. But only liraglutide has been given the go-ahead to treat obesity while semaglutide is currently being studied. Since both liraglutide and semaglutide are fatty acid acylated analogs of human GLP-1, their structures are identical. Semaglutide has a much longer half-life and full dipeptidyl peptidase-4 stability compared to ligandutide, which largely lowers calorie intake.

    In comparison to other GLP-1RAs, semaglutide was found to produce up to three times higher weight loss in type 2 diabetic patients and up to twice as much weight loss in obese patients, with some patients losing up to 15 kg. Clinical trials have also shown that semaglutide reduced energy intake by 25% over three meals while liraglutide reduced energy intake by 15% over one meal. Additionally, semaglutide lowered cardiovascular risk in patients with diabetes. Semaglutide is currently being investigated in two large phase III clinical trial programs for treating obesity: the STEP program, which aims to obtain regulatory approval for semaglutide as an anti-obesity drug and is evaluating cardiovascular outcomes in 17,500 patients. The researchers discovered that semaglutide causes weight loss without affecting energy expenditure through altering food preferences and dietary consumption.

    Semaglutide does not cross the blood-brain barrier, yet it directly targets the brainstem, septal nucleus, and hypothalamus. Instead, it communicates with the brain by means of the structures that surround the ventricles and a few specific locations nearby. In addition, semaglutide causes central c-Fos activation in eleven brain regions, including secondary regions devoid of direct GLP-1R interaction and portions of the hindbrain that are directly targeted by the drug.

    Based on the findings, the researchers suggest that semaglutide lowers body weight by directly interacting with diverse GLP-1R populations and directly and indirectly affecting the activity of neural pathways involved in food intake, reward, and energy expenditure. Transcriptomic analysis of microdissected brain areas from semaglutide-treated rats also showed upregulation of prolactin-releasing hormone and tyrosine hydroxylase in the area postrema (part of the brainstem).

15. Lingvay, I., Hansen, T., Macura, S., Marre, M., Nauck, M. A., de la Rosa, R., Woo, V., Yildirim, E., & Wilding, J. (2020). Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events. BMJ open diabetes research & care, 8(2), e001706. https://doi.org/10.1136/bmjdrc-2020-001706.
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    Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events

    The usage of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been linked to adverse events (AEs). Researchers discovered that gastrointestinal AEs are the most often reported AEs associated with these medications. People who use GLP-1RAs and have GI AEs typically lose a little bit more weight than those who do not.

    When compared to other GLP-1RA treatments, once-weekly semaglutide caused a larger weight loss, according to a previous study of the SUSTAIN 1-5 trials. In the SUSTAIN 3, 7, and 10 trials, semaglutide was found to be superior to other GLP-1RAs at lowering glycated hemoglobin and body weight. The goal of the study was to ascertain whether GI adverse events (GI AEs), such as nausea/vomiting, diarrhea, constipation, and dyspepsia (indigestion), during the dose escalation phase (baseline to week 12) and from baseline to the end of treatment, are responsible for the greater weight loss seen with semaglutide compared to other GLP-1RAs. The individuals in each trial were split into groups based on whether they reported having nausea, vomiting, or any other GI AE. The change in body weight was evaluated by the researchers, who then used mediation analysis to distinguish between the direct and indirect effects of weight reduction (mediated by GI AEs).

    The results showed that in the SUSTAIN 3, 7, and 10 trials, nausea/vomiting during dose escalation or throughout treatment contributed minimally (<0.1 kg) to the superior weight loss seen with semaglutide compared to GLP-1RA comparators at the end of treatment. Therefore, the researchers concluded that the greater weight loss seen with semaglutide compared to other GLP-1RAs is not primarily mediated by GI AEs, including nausea/vomiting, but rather by other direct effects of the drug.

16. Ard, J., Fitch, A., Fruh, S., & Herman, L. (2021). Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. Advances in therapy, 38(6), 2821–2839. https://doi.org/10.1007/s12325-021-01710-0.
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    Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists

    Obesity is a chronic condition that has a number of problems. A weight decrease of 5–15% of body weight can help reduce several obesity-related problems. Despite these benefits, it might be difficult to lose weight and keep it off for an extended period of time. Pharmacotherapy can help obese people lose the weight they want and keep it off, which can reduce the risk of obesity-related problems.

    In the United States, the prevalence of obesity has risen in recent decades, and while approved anti-obesity medications (AOMs) are available, the usage rate of these treatments may not match the disease’s prevalence. Researchers have identified several reasons for the low initiation and long-term use of AOMs, such as reluctance from public health and medical organizations to acknowledge obesity as a disease, a lack of reimbursement, provider inexperience, and misunderstandings about the effectiveness and safety of available treatments.

    A review of studies educated primary care providers about the mechanism of action of GLP-1 receptor agonists (GLP-1RAs), a type of AOM, in weight loss and the long-term maintenance of weight loss, as well as the effectiveness and safety of this medication class. GLP-1RA therapy was originally developed to treat type 2 diabetes but it has proven effective in reducing body weight, leading to the approval of liraglutide 3.0 mg for once-daily subcutaneous administration and the investigation of semaglutide 2.4 mg for once-weekly subcutaneous administration in phase III trials for obesity management. The review found that GLP-1RA-mediated weight loss can be achieved through several pathways including effects on the central nervous system such as increased feelings of satiety, reduced energy intake, and impaired food preferences. In addition, it was also found that the risk of adverse events associated with GLP-1RAs was higher but mild-to-moderate and transient. These adverse events are not the main reason for observed weight loss during treatment with GLP-1RAs.

    Overall, GLP-1RAs have higher safety, efficacy, and tolerability in obese patients and this treatment is associated with maintenance of body weight reductions of 5–10%. Therefore, the treatment can improve complications associated with obesity in addition to its weight-loss effects.

17. Johansen, P., Chubb, B., Hunt, B., Malkin, S., Sandberg, A., &Capehorn, M. (2020). Evaluating the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes in the UK. Advances in therapy, 37(5), 2427–2441. https://doi.org/10.1007/s12325-020-01337-7.
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    Evaluating the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes in the UK

    In the SUSTAIN 10 study, once-weekly semaglutide 1 mg, a novel GLP-1 RA, was shown to be more effective than once-daily liraglutide 1.2 mg at lowering HbA1c and body weight, according to the researchers. This study’s objective was to examine the long-term cost-effectiveness of once-weekly semaglutide 1 mg with once-daily liraglutide 1.2 mg from the viewpoint of a UK healthcare payer.

    In the base-case analysis, the researchers found that once-weekly semaglutide 1 mg led to a higher discounted life expectancy of 0.21 years and a higher discounted quality-adjusted life expectancy of 0.30 quality-adjusted life years compared to once-daily liraglutide 1.2 mg. The study showed that once-weekly semaglutide 1 mg was associated with cost savings of GBP 140 per patient, owing to a reduction in diabetes-related complications, particularly cardiovascular disease (with an average cost saving of GBP 279 per patient). Therefore, once-weekly semaglutide 1 mg was deemed superior to once-daily liraglutide 1.2 mg, as it provided clinical benefits at a lower cost.

    The sensitivity analyses conducted by the researchers showed similar results, indicating the robustness of the base-case analysis. The researchers concluded that once-weekly semaglutide 1 mg was a cost-effective treatment option compared to once-daily liraglutide 1.2 mg, based on the SUSTAIN 10 trial, from the perspective of a UK healthcare payer.

18. Johansen, P., Håkan-Bloch, J., Liu, A. R., Bech, P. G., Persson, S., &Leiter, L. A. (2019). Cost Effectiveness of Once-Weekly Semaglutide Versus Once-Weekly Dulaglutide in the Treatment of Type 2 Diabetes in Canada. PharmacoEconomics – open, 3(4), 537–550. https://doi.org/10.1007/s41669-019-0131-6.
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    Cost Effectiveness of Once-Weekly Semaglutide Versus Once-Weekly Dulaglutide in the Treatment of Type 2 Diabetes in Canada

    The researchers evaluated the cost-effectiveness of semaglutide in comparison to dulaglutide for the treatment of type 2 diabetes (T2D) when added to metformin monotherapy from a Canadian societal perspective. To achieve this, they employed the Swedish Institute for Health Economics Cohort Model of T2D. This model was used to analyze the cost-effectiveness of once-weekly semaglutide (0.5 or 1.0 mg) versus once-weekly dulaglutide (0.75 or 1.5 mg) over a 40-year period.

    In this study, the researchers used data from the SUSTAIN 7 trial to conduct a deterministic base-case analysis and scenario simulation. The results showed that semaglutide was more effective than dulaglutide at lowering systolic blood pressure, body mass index, and glycated hemoglobin (HbA1c). They also performed 15 deterministic sensitivity analyses and 15 probabilistic sensitivity analyses to assess the robustness of their findings. The results of the study showed that, in the base-case analysis, semaglutide was a more prevalent treatment option than dulaglutide. In comparison to dulaglutide, semaglutide was likewise linked to decreased overall expenses for both low-dose and high-dose therapies. Semaglutide was therefore determined to be a cost-effective therapeutic choice for T2D patients whose condition was not sufficiently controlled by metformin alone from a Canadian social standpoint.

    In conclusion, the researchers found that semaglutide was a more cost-effective treatment option for T2D patients compared with dulaglutide when added to metformin monotherapy, as it was associated with lower costs and superior clinical outcomes. The findings of this study could have implications for healthcare providers, policymakers, and patients with T2D who are seeking cost-effective treatment options.

19. Capehorn, M., Hallén, N., Baker-Knight, J., Glah, D., & Hunt, B. (2021). Evaluating the Cost-Effectiveness of Once-Weekly Semaglutide 1 mg VersusEmpagliflozin 25 mg for Treatment of Patients with Type 2 Diabetes in the UK Setting. Diabetes therapy : research, treatment and education of diabetes and related disorders, 12(2), 537–555. https://doi.org/10.1007/s13300-020-00989-6.
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    Evaluating the Cost-Effectiveness of Once-Weekly Semaglutide 1 mg Versus Empagliflozin 25 mg for Treatment of Patients with Type 2 Diabetes in the UK Setting

    In the past, researchers evaluated the cost-effectiveness of once-weekly semaglutide 1 mg versus empagliflozin 25 mg for treating type 2 diabetes mellitus patients who had insufficient glycemic (blood sugar) control on metformin monotherapy in the UK. Using the IQVIA CORE Diabetes Model, the researchers predicted outcomes throughout the patients’ lifetimes. Since there was no direct clinical study comparing the two treatments head-to-head, the baseline cohort characteristics and treatment outcomes of once-weekly semaglutide 1 mg and empagliflozin 25 mg were based on an indirect comparison utilizing patient-level data.

    The modeled patients received treatment until glycated hemoglobin exceeded 7.5% (58 mmol/mol), at which point they initiated basal insulin. The analysis captured pharmacy costs and the costs of diabetes-related complications expressed in 2019 pounds sterling (GBP). The researchers discounted projected outcomes at 3.5% annually and prepared scenario analyses to assess the uncertainty around projected outcomes. The analysis’s findings demonstrated that when compared to empagliflozin 25 mg, once-weekly semaglutide 1 mg was linked with increases in life expectancy and quality-adjusted life expectancy of 0.12 years and 0.23 QALYs, respectively. Reduced cumulative incidence and postponed onset of diabetes-related problems are what led to the anticipated increases in life quality and longevity. Once-weekly semaglutide was linked to higher pharmacy expenditures, however, this was somewhat compensated by the avoidance of complications-related medical expenses.

    The study’s findings revealed that once-weekly semaglutide was linked to a GBP 1017 rise in expenses per patient, resulting in an additional cost-effectiveness ratio of GBP 4439 for every QALY gained. Based on their analysis, the researchers concluded that once-weekly semaglutide 1 mg was a cost-effective treatment option from a healthcare payer perspective compared to empagliflozin 25 mg for treating patients with type 2 diabetes in the UK setting.

20. Ericsson, Å.,&Fridhammar, A. (2019). Cost-effectiveness of once-weekly semaglutide versus dulaglutide and lixisenatide in patients with type 2 diabetes with inadequate glycemic control in Sweden. Journal of medical economics, 22(10), 997–1005. https://doi.org/10.1080/13696998.2019.1614009.
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    Cost-effectiveness of once-weekly semaglutide versus dulaglutide and lixisenatide in patients with type 2 diabetes with inadequate glycemic control in Sweden

    Researchers in Sweden evaluated the cost-effectiveness of once-weekly semaglutide against glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) who were not responsive to either metformin or basal insulin. This cost-effectiveness analysis (CEA) made use of the Diabetes Cohort Model from the Swedish Institute of Health Economics (IHE). Over a 40-year period, the examination was done from the standpoint of Swedish society.

    For patients uncontrolled on metformin, the researchers used dulaglutide as the comparator and obtained data from the SUSTAIN 7 clinical trial. For patients uncontrolled on basal insulin, lixisenatide was selected as the comparator, and data were obtained from a network meta-analysis. The researchers found that in patients with inadequate control of metformin, semaglutide 1.0 mg provided greater clinical benefit and was less expensive than dulaglutide 1.5 mg, which means it dominated dulaglutide. Similarly, in patients with inadequate control of basal insulin, semaglutide 1.0 mg dominated lixisenatide. The researchers noted that the reduction in costs was mainly due to the reduction in complications seen with once-weekly semaglutide. They also pointed out that the analysis may have underestimated the cardiovascular (CV) cost benefits associated with treatment with once-weekly semaglutide. Due to the lack of a head-to-head clinical study for this comparison, evaluations versus lixisenatide for patients with poorly regulated basal insulin were based on NMA findings.

    The researchers concluded that once-weekly semaglutide is a GLP-1 RA medication that is cost-effective for treating T2D in patients who are insufficiently managed by metformin or basal insulin. The treatment can help address many of the unmet demands of Swedish clinicians, patients, and payers at the moment.

21. Viljoen, A., Hoxer, C. S., Johansen, P., Malkin, S., Hunt, B., & Bain, S. C. (2019). Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK. Diabetes, obesity & metabolism, 21(3), 611–621. https://doi.org/10.1111/dom.13564.
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    Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK

    A group of researchers evaluated the long-term cost-effectiveness of two once-weekly glucagon-like peptide-1 (GLP-1) receptor agonists, semaglutide 0.5 and 1 mg, in comparison to dulaglutide 1.5 mg in people with type 2 diabetes mellitus (T2DM) in the UK healthcare system. The research was based on the SUSTAIN 7 trial, a head-to-head comparison meant to aid in healthcare decision-making.

    The study found that both doses of once-weekly semaglutide improved quality-adjusted life expectancy compared to dulaglutide. Semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.04 and 0.10 quality-adjusted life years, respectively. Moreover, the clinical benefits of semaglutide were achieved at a lower cost, resulting in lifetime cost savings of GBP 35 for semaglutide 0.5 mg and GBP 106 for semaglutide 1 mg, due to fewer diabetes-related complications resulting from better glycemic control. Because they produced better results and were less expensive than dulaglutide 1.5 mg, the once-weekly semaglutide doses were deemed dominant. Since once-weekly semaglutide is a cost-effective alternative for T2DM patients in the UK who are not controlling their blood sugar with metformin, it is expected to enhance clinical results and lower costs.

    In conclusion, the researchers found that once-weekly semaglutide was a cost-effective treatment option for individuals with T2DM in the UK healthcare system. Semaglutide not only improved quality-adjusted life expectancy but also reduced costs due to better glycemic control and fewer diabetes-related complications. This study provides important information for healthcare decision-makers in the UK regarding the optimal treatment for individuals with T2DM who are not achieving glycemic control with metformin.

22. Gorgojo-Martínez, J. J., Malkin, S., Martín, V., Hallén, N., & Hunt, B. (2020). Assessing the cost-effectiveness of a once-weekly GLP-1 analogue versus an SGLT-2 inhibitor in the Spanish setting: Once-weekly semaglutide versus empagliflozin. Journal of medical economics, 23(2), 193–203. https://doi.org/10.1080/13696998.2019.1681436.
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    Assessing the cost-effectiveness of a once-weekly GLP-1 analogue versus an SGLT-2 inhibitor in the Spanish setting: Once-weekly semaglutide versus empagliflozin

    By evaluating the cost-effectiveness of two different drugs for the treatment of type 2 diabetes (T2D) patients in the Spanish setting who had insufficient glycemic control on oral anti-hyperglycemic medications, a group of researchers addressed the challenge of balancing healthcare gains with costs. They compared the cost-effectiveness of subcutaneous once-weekly semaglutide (0.5 mg and 1 mg) to empagliflozin (10 mg and 25 mg) over the long run.

    To do this, the researchers used the IQVIA CORE Diabetes Model to project outcomes over patient lifetimes with once-weekly semaglutide versus empagliflozin. They based their treatment effects on a network meta-analysis and captured treatment costs, costs of diabetes-related complications, and the impact of complications on quality of life using published sources. They discounted outcomes at 3.0% per annum. The results showed that both once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy compared to empagliflozin 10 mg and 25 mg. Specifically, once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted quality-adjusted life expectancy of 0.12 and 0.15 quality-adjusted life years (QALYs), respectively, versus empagliflozin 10 mg, and improvements of 0.11 and 0.14 QALYs, respectively, versus empagliflozin 25 mg. When compared to empagliflozin, once-weekly semaglutide had greater treatment costs but the researchers found that this was somewhat offset by cost savings from avoiding complications associated with diabetes. In particular, compared to empagliflozin 10 mg, once-weekly semaglutide 0.5 mg and 1 mg were associated with incremental cost-effectiveness ratios of EUR 2,285 and EUR 161 per QALY gained, respectively, and EUR 3,090 and EUR 625 per QALY gained, respectively.

    In conclusion, based on a willingness-to-pay threshold of EUR 30,000 per QALY gained, the researchers projected that once-weekly semaglutide 0.5 mg and 1 mg were cost-effective compared to empagliflozin 10 mg and 25 mg for the treatment of patients with T2D with inadequate glycemic control on oral anti-hyperglycemic medications in the Spanish setting, regardless of patients’ BMI at baseline.

23. Ruan, Z., Yang, L., Shi, H., Yue, X., Wang, Y., Liang, M., &Hu, H. (2021). The cost-effectiveness of once-weekly semaglutide compared with other GLP-1 receptor agonists in type 2 Diabetes: a systematic literature review. Expert review of pharmacoeconomics& outcomes research, 21(2), 221–233. https://doi.org/10.1080/14737167.2021.1860022.
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    The cost-effectiveness of once-weekly semaglutide compared with other GLP-1 receptor agonists in type 2 Diabetes: a systematic literature review

    Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) and innovative treatment for type 2 diabetes (T2D), has been assessed for its economic value in a number of nations. In order to shed light on future research, researchers set out to thoroughly review the most recent pharmacoeconomic literature on the cost-effectiveness of once-weekly semaglutide in comparison to other GLP-1 RAs.

    To accomplish this, a systematic literature review of cost-effectiveness analyses (CEA) comparing once-weekly semaglutide to other GLP-1 RAs in T2D was conducted. The study searched PubMed, Web of Science, and the ISPOR presentation database for articles published up to 25 July 2020. Nineteen studies were identified, including eight short-term and 11 long-term studies, and their general characteristics and main results were summarized. The review provided references for other countries to understand the value of once-weekly semaglutide compared to other GLP-1 RAs in T2D in the healthcare decision-making process and to conduct their own CEA studies related to once-weekly semaglutide. The authors found that current studies underestimated the cardiovascular (CV) benefits of once-weekly semaglutide and suggested that methods for economic evaluations of novel anti-diabetic drugs with CV benefits should be improved in future research.

    In conclusion, once-weekly semaglutide’s economic worth in comparison to other GLP-1 RAs has been evaluated in a number of nations and this systematic evaluation adds to the understanding of the drug’s cost-effectiveness. The results of the analysis could be used to inform future studies on the economic benefits of once-weekly semaglutide as well as healthcare decision-making procedures. The necessity for continuous research in this area is highlighted by the authors’ advice to enhance procedures for economic analyses of novel anti-diabetic medications with CV advantages.

24. Vidal, J., Malkin, S., Hunt, B., Martín, V., Hallén, N., & Javier Ortega, F. (2020). The Short-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Sitagliptin and Once-Weekly Dulaglutide for the Treatment of Patients with Type 2 Diabetes: A Cost of Control Analysis in Spain. Diabetes therapy : research, treatment and education of diabetes and related disorders, 11(2), 509–521. https://doi.org/10.1007/s13300-019-00751-7.
    View Summary +

    The Short-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Sitagliptin and Once-Weekly Dulaglutide for the Treatment of Patients with Type 2 Diabetes: A Cost of Control Analysis in Spain

    The researchers conducted a study aimed at optimizing care for patients with type 2 diabetes by achieving glycemic control targets, preventing weight gain, and avoiding hypoglycemic events using modern interventions like GLP-1 receptor agonists and DPP4 inhibitors. They recognized that healthcare payers are concerned about the increasing prevalence of type 2 diabetes and need interventions that achieve these aims in a cost-effective manner.

    In a trial of individuals with type 2 diabetes in Spain, the researchers compared the cost-effectiveness of semaglutide, sitagliptin, and dulaglutide. They assessed the effectiveness of the treatments in terms of lowering glycated hemoglobin (HbA1c), body weight, and the percentage of patients meeting treatment goals using data from the SUSTAIN 2 and 7 clinical trials. The study found that both doses of semaglutide were associated with lower costs of control for all three endpoints compared to sitagliptin and dulaglutide 1.5 mg. When endpoints incorporating hypoglycemia (low blood sugar) and weight loss alongside glycemic control were considered, semaglutide had comparable or lower costs of control than sitagliptin. Additionally, semaglutide had lower costs of control than dulaglutide 1.5 mg for all endpoints.

    In conclusion, the study raises the possibility that semaglutide may be a more affordable treatment choice for individuals with type 2 diabetes in Spain than sitagliptin and dulaglutide, especially when taking into account outcomes like hypoglycemia and weight loss in addition to glycemic control.

25. Hunt, B., Malkin, S., Moes, R., Huisman, E. L., Vandebrouck, T., &Wolffenbuttel, B. (2019). Once-weekly semaglutide for patients with type 2 diabetes: a cost-effectiveness analysis in the Netherlands. BMJ open diabetes research & care, 7(1), e000705. https://doi.org/10.1136/bmjdrc-2019-000705.
    View Summary +

    Once-weekly semaglutide for patients with type 2 diabetes: a cost-effectiveness analysis in the Netherlands

    Choosing safe and effective treatments for type 2 diabetes is vital in order to maximize the health of affected individuals. In order to help healthcare systems around the world reach this goal, researchers sought to identify type 2 diabetes treatments that are both efficient and affordable.

    In the Netherlands, they carried out an analysis to compare the once-weekly GLP-1 receptor agonist semaglutide with dulaglutide, a different once-weekly GLP-1 receptor agonist, and insulin glargine U100, the most widely used basal insulin, in terms of cost-effectiveness. To project outcomes for once-weekly semaglutide 0.5 mg and 1 mg versus insulin glargine U100, once-weekly semaglutide 0.5 mg versus dulaglutide 0.75 mg, and once-weekly semaglutide 1 mg versus dulaglutide 1.5 mg, the researchers utilized the IQVIA CORE Diabetes Model. They sourced clinical data from the SUSTAIN 4 and SUSTAIN 7 clinical trials. The analysis captured direct and indirect costs, mortality, and the impact of diabetes-related complications on the quality of life. The researchers’ projections of outcomes over patient lifetimes suggest that once-weekly semaglutide 0.5 mg and 1 mg are likely to improve clinical outcomes for patients with type 2 diabetes compared to insulin glargine U100 and dulaglutide. Improvements in clinical outcomes compared to insulin glargine U100 were observed at an increased cost but once-weekly semaglutide was still deemed cost-effective even at the lowest willingness-to-pay threshold identified in the Netherlands.

    From a societal perspective, improvements were observed at a reduced cost versus dulaglutide, and therefore once-weekly semaglutide was considered dominant. Semaglutide used once a week is more affordable than insulin glargine U100 and superior to dulaglutide 0.75 and 1.5 mg for the treatment of type 2 diabetes, according to the study’s findings. The usage of once-weekly semaglutide was cited as an effective way for the Netherlands to use its healthcare resources.

26. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.
    View Summary +

    Once-Weekly Semaglutide in Adults with Overweight or Obesity

    The goal of the study was to determine whether once-weekly administration of semaglutide at a dose of 2.4 mg as a supplement to lifestyle changes could help adults with obesity lose weight. In a double-blind trial, they enrolled 1961 adults with a body mass index (BMI) of 30 or higher who were free of diabetes. Along with a lifestyle intervention, the participants were randomly assigned to receive either a placebo or once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) for 68 weeks.

    The researchers used two primary endpoints to assess the effectiveness of the treatment: the percentage change in body weight and weight reduction of at least 5%. The primary estimand evaluated the treatment effects regardless of treatment discontinuation or rescue interventions. The researchers found that participants who received semaglutide had a greater improvement in cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received a placebo. The most common adverse events associated with semaglutide were nausea and diarrhea, which were typically transient and mild-to-moderate in severity and subsided with time. However, more participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events.

    In conclusion, the researchers discovered that in patients with overweight or obesity, 2.4 mg of semaglutide once weekly combined with lifestyle modification was associated with persistent, clinically significant weight loss. These discoveries offer fresh pharmaceutical possibilities for the global health problem of obesity.

27. O’Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16. PMID: 30122305.
    View Summary +

    Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial

    Obesity was recognized as a significant public health issue. Because of this, more new treatment options are needed to achieve and sustain a healthy weight in affected individuals.

    A group of researchers investigated the effectiveness and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide for weight management. To accomplish this, they conducted a phase 2 trial that was randomized, double-blind, placebo and active- controlled, multicentre, and dose-ranging. The study was conducted in eight countries, and 71 clinical sites were involved. Adults without diabetes who met the eligibility requirements participated in the trial. The semaglutide, liraglutide, or corresponding placebo groups were the active therapy groups that the researchers randomly assigned the subjects to. To assure randomness, a block size of 56 was employed. With the exception of the target dose, all doses of the medication were given once daily by subcutaneous injection, and both the participants and the researchers were unaware of the assigned study treatment. The primary endpoint of the study was the percentage of weight loss at week 52. The researchers analyzed the data using intention-to-treat ANCOVA estimation and the missing data was derived from the placebo pool. All semaglutide doses were generally well tolerated, and there were no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, as previously seen with GLP-1 receptor agonists.

    The researchers concluded that semaglutide, in combination with dietary and physical activity counseling, was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses. The results of this study suggest that semaglutide may be a promising pharmaceutical treatment option for weight management.

28. Andreadis P, Karagiannis T, Malandris K, Avgerinos I, Liakos A, Manolopoulos A, Bekiari E, Matthews DR, Tsapas A. Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes ObesMetab. 2018 Sep;20(9):2255-2263. doi: 10.1111/dom.13361. Epub 2018 Jun 10. PMID: 29756388.
    View Summary +

    Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis

    In this study, researchers assessed the effectiveness and safety of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), for the treatment of type 2 diabetes. They conducted a comprehensive search in electronic databases and grey literature sources to identify randomized controlled trials comparing semaglutide with placebo or other antidiabetic medications. The primary objective was to measure the change in HbA1c from baseline, while secondary endpoints included changes in body weight, blood pressure, heart rate, incidence of hypoglycemia (low blood sugar levels), gastrointestinal side effects, pancreatitis, and diabetic retinopathy (an eye complication of diabetes).

    The researchers included a total of 6 placebo-controlled studies and 7 studies comparing semaglutide with other antidiabetic drugs administered subcutaneously. They found only one trial that investigated the use of oral semaglutide. Both doses of subcutaneous semaglutide demonstrated superior efficacy in lowering blood glucose (sugar) levels compared to other antidiabetic agents such as sitagliptin, exenatide, liraglutide, dulaglutide, and insulin glargine. Semaglutide also had a positive impact on body weight (compared to placebo for semaglutide 1 mg) and systolic blood pressure. The researchers did not observe an increased risk of hypoglycemia with semaglutide, but they noted a higher incidence of nausea, vomiting, and diarrhea. Pancreatitis cases were rare, and the odds ratio for diabetic retinopathy compared to placebo was 1.32.

    Based on their findings, the authors concluded that semaglutide is an effective weekly GLP-1 RA that significantly reduces systolic blood pressure, body weight, and HbA1c levels. However, it is associated with a higher occurrence of gastrointestinal adverse effects. They recommend further evaluation of the pancreatitis and retinopathy findings through post-approval pharmacovigilance studies.

29. Andersen A, Knop FK, Vilsbøll T. A Pharmacological and Clinical Overview of Oral Semaglutide for the Treatment of Type 2 Diabetes. Drugs. 2021 Jun;81(9):1003-1030. doi: 10.1007/s40265-021-01499-w. Epub 2021 May 8. PMID: 33964002; PMCID: PMC8217049.
    View Summary +

    A Pharmacological and Clinical Overview of Oral Semaglutide for the Treatment of Type 2 Diabetes

    The researchers of the study wanted to find better ways to manage type 2 diabetes and prevent complications. They aimed to control blood sugar levels, help patients lose weight, and manage their cardiovascular health. To do this, they studied different medications that could lower blood sugar levels effectively. One commonly used medication called metformin was often used as the first-line treatment, but many patients needed additional medications to control their blood sugar levels well. The choice of medication depended on factors like cost and the presence of other health problems.

    The researchers studied a new medication called oral semaglutide (Rybelsus®), which belongs to a class of drugs called GLP-1 receptor agonists. It is taken as a pill and is designed to help control blood sugar levels. Previous GLP-1 receptor agonists were given as injections, but this new one could be taken orally. The results of the study showed that oral semaglutide, either alone or in combination with other medications, effectively controlled blood sugar levels, helped with weight loss, and reduced high blood pressure. It had similar safety and side effects to other medications in its class. It rarely caused low blood sugar levels, and the most common side effects were nausea and diarrhea. The study also showed that oral semaglutide was safe for the heart, similar to taking a placebo (a fake pill), and its effects on the heart were likely similar to the injected form of semaglutide.

    GLP-1 receptor agonists should be more widely accepted by patients and healthcare professionals. When used as an early treatment for diabetes, it can produce beneficial effects on blood sugar levels, body weight, and blood pressure.

30. Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27. PMID: 34706925; PMCID: PMC8717485.
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    Wegovy (semaglutide): a new weight loss drug for chronic weight management.

    The provided reference is an article by Singh et al. titled “Wegovy (semaglutide): a new weight loss drug for chronic weight management.” The study was published in the Journal of Investigative Medicine in January 2022. The authors discuss Wegovy (semaglutide), a medication indicated for chronic weight management. The article provides an overview of semaglutide’s mechanism of action, clinical trials, efficacy in promoting weight loss, safety profile, and potential side effects. For more in-depth information, the publication can be accessed using the PMID: 34706925 and PMCID: PMC8717485.

31. Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619. PMID: 35015037; PMCID: PMC8753508.
    View Summary +

    Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes
    

    The provided reference is a study conducted by Rubino et al. titled “Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.” The study was published in JAMA (Journal of the American Medical Association) in January 2022. The authors aimed to compare the effects of weekly subcutaneous semaglutide with daily liraglutide on body weight in adults with overweight or obesity but without diabetes. The randomized clinical trial investigated the efficacy of these medications in promoting weight loss. The publication can be accessed for more detailed information using the PMID: 35015037 and PMCID: PMC8753508.

32. Mares AC, Chatterjee S, Mukherjee D. Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. CurrOpinCardiol. 2022 Feb 16. doi: 10.1097/HCO.0000000000000955. Epub ahead of print. PMID: 35175229.
    View Summary +

    Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity.
    

    The provided reference is an article by Mares et al. titled “Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity.” The article was published ahead of print in the journal Current Opinion in Cardiology on February 16, 2022. The authors discuss the use of semaglutide for weight loss and its potential in reducing cardiometabolic risk in individuals with overweight or obesity. The publication explores the current understanding of semaglutide’s efficacy in weight management and its impact on cardiometabolic parameters. For more detailed information, the article can be accessed using the PMID: 35175229.

33. Chao AM, Tronieri JS, Amaro A, Wadden TA. Semaglutide for the treatment of obesity. Trends Cardiovasc Med. 2021 Dec 21:S1050-1738(21)00158-4. doi: 10.1016/j.tcm.2021.12.008. Epub ahead of print. PMID: 34942372.
    View Summary +

    Semaglutide for the treatment of obesity
    

    The provided reference is an article by Chao et al. titled “Semaglutide for the treatment of obesity.” The article was published ahead of print in the journal Trends in Cardiovascular Medicine on December 21, 2021. The authors discuss the use of semaglutide as a treatment for obesity. The publication explores the current trends and developments in utilizing semaglutide for weight management, its efficacy, safety profile, and potential cardiovascular benefits. For more detailed information, the article can be accessed using the PMID: 34942372.

34. Zhong P, Zeng H, Huang M, Fu W, Chen Z. Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis. Endocrine. 2022 Mar;75(3):718-724. doi: 10.1007/s12020-021-02945-1. Epub 2022 Jan 4. PMID: 34981419.
    View Summary +

    Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis
    

    The provided reference is a meta-analysis conducted by Zhong et al. titled “Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis.” The study was published in the journal Endocrine in March 2022. The authors aimed to assess the efficacy and safety of once-weekly semaglutide in adults with overweight or obesity. By analyzing relevant studies, the meta-analysis provided insights into the effectiveness of semaglutide in promoting weight loss and its safety profile. For more detailed information, the publication can be accessed using the PMID: 34981419.

35. Andreadis, P., Karagiannis, T., Malandris, K., Avgerinos, I., Liakos, A., Manolopoulos, A., Bekiari, E., Matthews, D. R., &Tsapas, A. (2018). Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 20(9), 2255–2263. https://doi.org/10.1111/dom.13361.
    View Summary +

    Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.
    

    The provided reference is an article by Andreadis et al. titled “Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.” The study was published in the journal Diabetes, Obesity & Metabolism in 2018. The authors conducted a systematic review and meta-analysis to evaluate the efficacy of semaglutide in the treatment of type 2 diabetes mellitus. The publication provides a comprehensive overview of relevant studies and analyzes the data to assess the effectiveness and safety of semaglutide in managing type 2 diabetes. For more detailed information, the article can be accessed using the provided DOI: 10.1111/dom.13361.

36. Kadowaki, T., Isendahl, J., Khalid, U., Lee, S. Y., Nishida, T., Ogawa, W., Tobe, K., Yamauchi, T., Lim, S., & STEP 6 investigators (2022). Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. The lancet. Diabetes & endocrinology, 10(3), 193–206. https://doi.org/10.1016/S2213-8587(22)00008-0.
    View Summary +

    Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial.
    

    The provided reference is an article by Kadowaki et al. titled “Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial.” The study was published in The Lancet Diabetes & Endocrinology in 2022. The authors conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of once-weekly semaglutide in adults with overweight or obesity, with or without type 2 diabetes, in an East Asian population. The publication provides insights into the findings of the trial, including weight loss outcomes and the impact on cardiometabolic parameters. For more detailed information, the article can be accessed using the provided DOI: 10.1016/S2213-8587(22)00008-0.

37. Gao, X., Hua, X., Wang, X., Xu, W., Zhang, Y., Shi, C., & Gu, M. (2022). Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials. Frontiers in pharmacology, 13, 935823. https://doi.org/10.3389/fphar.2022.935823.
    View Summary +

    Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials.
    

    The provided reference is an article by Gao et al. titled “Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials.” The study was published in the journal Frontiers in Pharmacology in 2022. The authors conducted a systematic review and meta-analysis of randomized controlled trials to assess the effectiveness and safety of semaglutide in promoting weight loss in obese or overweight patients without diabetes. The publication provides an overview of the findings from the analyzed trials and offers insights into the potential benefits of semaglutide for weight management. For more detailed information, the article can be accessed using the provided DOI: 10.3389/fphar.2022.935823.

38. Lautenbach, A., Wernecke, M., Huber, T. B., Stoll, F., Wagner, J., Meyhöfer, S. M., Meyhöfer, S., & Aberle, J. (2022). The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery-a Retrospective Analysis. Obesity surgery, 32(10), 3280–3288. https://doi.org/10.1007/s11695-022-06211-9.
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    The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery-a Retrospective Analysis.
    

    The provided reference is an article by Lautenbach et al. titled “The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery – a Retrospective Analysis.” The study was published in the journal Obesity Surgery in 2022. The authors conducted a retrospective analysis to evaluate the potential of semaglutide once-weekly in patients without type 2 diabetes who experienced weight regain or insufficient weight loss after bariatric surgery. The publication explores the outcomes and effectiveness of using semaglutide in this patient population. For more detailed information, the article can be accessed using the provided DOI: 10.1007/s11695-022-06211-9.

39. Arastu, N., Cummins, O., Uribe, W., & Nemec, E. C. (2022). Efficacy of subcutaneous semaglutide compared to placebo for weight loss in obese, non-diabetic adults: a systematic review & meta-analysis. International journal of clinical pharmacy, 44(4), 852–859. https://doi.org/10.1007/s11096-022-01428-1.
    View Summary +

    Efficacy of subcutaneous semaglutide compared to placebo for weight loss in obese, non-diabetic adults: a systematic review & meta-analysis.
    

    The provided reference is an article by Arastu et al. titled “Efficacy of subcutaneous semaglutide compared to placebo for weight loss in obese, non-diabetic adults: a systematic review & meta-analysis.” The study was published in the International Journal of Clinical Pharmacy in 2022. The authors conducted a systematic review and meta-analysis to assess the efficacy of subcutaneous semaglutide compared to placebo in promoting weight loss in obese, non-diabetic adults. The publication provides insights into the findings from the analyzed studies and offers an overview of the potential benefits of semaglutide for weight management in this population. For more detailed information, the article can be accessed using the provided DOI: 10.1007/s11096-022-01428-1.

40. Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O’Neil, P. M., Rubino, D. M., Skovgaard, D., Wallenstein, S. O. R., Garvey, W. T., & STEP 3 Investigators (2021). Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA, 325(14), 1403–1413. https://doi.org/10.1001/jama.2021.1831.
    View Summary +

    Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.
    

    The provided reference is an article by Wadden et al. titled “Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.” The study was published in JAMA (Journal of the American Medical Association) in 2021. The authors conducted a randomized clinical trial (STEP 3) to evaluate the effect of subcutaneous semaglutide compared to placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity. The publication provides insights into the findings of the trial, including the impact of semaglutide on weight loss outcomes. For more detailed information, the article can be accessed using the provided DOI: 10.1001/jama.2021.1831.

41. Ghusn, W., De la Rosa, A., Sacoto, D., Cifuentes, L., Campos, A., Feris, F., Hurtado, M. D., & Acosta, A. (2022). Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. JAMA network open, 5(9), e2231982. https://doi.org/10.1001/jamanetworkopen.2022.31982.
    View Summary +

    Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity.
    

    The provided reference is an article by Ghusn et al. titled “Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity.” The study was published in JAMA Network Open in 2022. The authors conducted a study to evaluate the weight loss outcomes associated with semaglutide treatment in patients with overweight or obesity. The publication presents the findings of the study, shedding light on the effectiveness of semaglutide in promoting weight loss in this patient population. For more detailed information, the article can be accessed using the provided DOI: 10.1001/jamanetworkopen.2022.31982.

42. Mishriky, B. M., Cummings, D. M., Powell, J. R., Sewell, K. A., & Tanenberg, R. J. (2019). Comparing once-weekly semaglutide to incretin-based therapies in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes & metabolism, 45(2), 102–109. https://doi.org/10.1016/j.diabet.2018.09.002.
    View Summary +

    Comparing once-weekly semaglutide to incretin-based therapies in patients with type 2 diabetes: a systematic review and meta-analysis.
    

    The provided reference is an article by Mishriky et al. titled “Comparing once-weekly semaglutide to incretin-based therapies in patients with type 2 diabetes: a systematic review and meta-analysis.” The study was published in the journal Diabetes & Metabolism in 2019. The authors conducted a systematic review and meta-analysis to compare the effectiveness of once-weekly semaglutide with incretin-based therapies in patients with type 2 diabetes. The publication presents the findings of the analysis, providing insights into the relative benefits and outcomes of these treatment approaches. For more detailed information, the article can be accessed using the provided DOI: 10.1016/j.diabet.2018.09.002.

43. Andreadis, P., Karagiannis, T., Malandris, K., Avgerinos, I., Liakos, A., Manolopoulos, A., Bekiari, E., Matthews, D. R., &Tsapas, A. (2018). Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 20(9), 2255–2263. https://doi.org/10.1111/dom.13361.
    View Summary +

    Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.

    The provided reference is an article by Andreadis et al. titled “Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.” The study was published in the journal Diabetes, Obesity & Metabolism in 2018. The authors conducted a systematic review and meta-analysis to evaluate the effectiveness of semaglutide for the treatment of type 2 diabetes mellitus. The publication presents the findings of the analysis, providing insights into the efficacy of semaglutide in managing type 2 diabetes. For more detailed information, the article can be accessed using the provided DOI: 10.1111/dom.13361.

44. Hedrington, M. S., & Davis, S. N. (2019). Oral semaglutide for the treatment of type 2 diabetes. Expert opinion on pharmacotherapy, 20(2), 133–141. https://doi.org/10.1080/14656566.2018.1552258.
    View Summary +

    Oral semaglutide for the treatment of type 2 diabetes Expert opinion on pharmacotherapy, 20(2), 133–141
    

    The provided reference is an article by Hedrington and Davis titled “Oral semaglutide for the treatment of type 2 diabetes.” The study was published in the journal Expert Opinion on Pharmacotherapy in 2019. The authors provide an expert opinion on the use of oral semaglutide as a treatment option for type 2 diabetes. The publication discusses the efficacy and safety profile of oral semaglutide, as well as its potential role in the management of type 2 diabetes. For more detailed information, the article can be accessed using the provided DOI: 10.1080/14656566.2018.1552258.

45. Anderson, S. L., Beutel, T. R., & Trujillo, J. M. (2020). Oral semaglutide in type 2 diabetes. Journal of diabetes and its complications, 34(4), 107520. https://doi.org/10.1016/j.jdiacomp.2019.107520.
    View Summary +

    Oral semaglutide in type 2 diabetes. Journal of diabetes and its complications, 34(4), 107520

    The provided reference is an article by Anderson, Beutel, and Trujillo titled “Oral semaglutide in type 2 diabetes.” The study was published in the Journal of Diabetes and its Complications in 2020. The authors discuss the use of oral semaglutide as a treatment option for type 2 diabetes. The publication provides an overview of the efficacy and safety of oral semaglutide, as well as its potential benefits and considerations in clinical practice. For more detailed information, the article can be accessed using the provided DOI: 10.1016/j.jdiacomp.2019.107520.

46. Avgerinos, I., Michailidis, T., Liakos, A., Karagiannis, T., Matthews, D. R., Tsapas, A., &Bekiari, E. (2020). Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 22(3), 335–345. https://doi.org/10.1111/dom.13899.
    View Summary +

    Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis.

    The reference you provided is an article by Avgerinos, Michailidis, Liakos, Karagiannis, Matthews, Tsapas, and Bekiari titled “Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis.” The study was published in Diabetes, Obesity & Metabolism in 2020. The authors conducted a systematic review and meta-analysis to assess the efficacy and safety of oral semaglutide for the treatment of type 2 diabetes. The article provides a comprehensive analysis of available evidence and discusses the potential benefits and considerations of using oral semaglutide in clinical practice. For more detailed information, you can access the article using the provided DOI: 10.1111/dom.13899.

47. Goldenberg, R. M., & Steen, O. (2019). Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes. Canadian journal of diabetes, 43(2), 136–145. https://doi.org/10.1016/j.jcjd.2018.05.008.
    View Summary +

    Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes.
    

    The reference you provided is an article by Goldenberg and Steen titled “Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes.” The article was published in the Canadian Journal of Diabetes in 2019. The authors provide a comprehensive review of semaglutide and its role in the treatment of type 2 diabetes. They discuss the pharmacology, efficacy, safety, and clinical considerations of semaglutide, as well as its place in therapy compared to other treatment options. The article aims to provide healthcare professionals with valuable insights into the use of semaglutide for adults with type 2 diabetes. For more detailed information, you can access the article using the provided DOI: 10.1016/j.jcjd.2018.05.008.

48. Brown, R. E., Bech, P. G., & Aronson, R. (2020). Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study). Diabetes, obesity & metabolism, 22(11), 2013–2020. https://doi.org/10.1111/dom.14117.
    View Summary +

    Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study).
    

    The reference you provided is an article by Brown, Bech, and Aronson titled “Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study).” The article was published in Diabetes, Obesity & Metabolism in 2020. The authors conducted a real-world analysis using data from the Canadian LMC Diabetes Registry to evaluate the effectiveness and safety of once-weekly semaglutide in people with type 2 diabetes. They assessed glycemic control, body weight changes, and the incidence of adverse events in a large cohort of patients. The study provides valuable insights into the real-world use of semaglutide and its impact on diabetes management. For more detailed information, you can access the article using the provided DOI: 10.1111/dom.14117.

49. Li, J., He, K., Ge, J., Li, C., & Jing, Z. (2021). Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes research and clinical practice, 172, 108656. https://doi.org/10.1016/j.diabres.2021.108656.
    View Summary +

    Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.
    

    The reference you provided is an article by Li, He, Ge, Li, and Jing titled “Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.” The article was published in Diabetes Research and Clinical Practice in 2021. The authors conducted a systematic review and meta-analysis to evaluate the efficacy and safety of oral semaglutide, a glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes mellitus. They analyzed data from relevant clinical trials and assessed outcomes such as glycemic control, body weight changes, and adverse events. The study provides a comprehensive overview of the available evidence on the use of oral semaglutide in the management of type 2 diabetes. For more detailed information, you can access the article using the provided DOI: 10.1016/j.diabres.2021.108656.

50. Araki E, Terauchi Y, Watada H, Deenadayalan S, Christiansen E, Horio H, Kadowaki T. Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials. Diabetes ObesMetab. 2021 Dec;23(12):2785-2794. doi: 10.1111/dom.14536. Epub 2021 Sep 27. PMID: 34472698.
    View Summary +

    Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials.
    

    The reference you provided is an article by Araki, Terauchi, Watada, Deenadayalan, Christiansen, Horio, and Kadowaki titled “Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4, and 8 trials.” The article was published in Diabetes, Obesity & Metabolism in 2021. The authors conducted a post hoc subgroup analysis of the PIONEER trials, which evaluated the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes. They analyzed data from the PIONEER 1, 3, 4, and 8 trials and assessed outcomes such as glycemic control, body weight changes, and adverse events specifically in the Japanese patient population. The study provides insights into the use of oral semaglutide in Japanese patients with type 2 diabetes. For more detailed information, you can access the article using the provided DOI: 10.1111/dom.14536.

51. Okamoto A, Yokokawa H, Nagamine T, Fukuda H, Hisaoka T, Naito T. Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists. J Diabetes MetabDisord. 2021 Sep 25;20(2):2121-2128. doi: 10.1007/s40200-021-00899-9. PMID: 34900848; PMCID: PMC8630305.
    View Summary +

    Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists.
    

    The reference you provided is an article by Okamoto, Yokokawa, Nagamine, Fukuda, Hisaoka, and Naito titled “Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles, and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists.” The article was published in the Journal of Diabetes & Metabolic Disorders in 2021. The authors conducted a study to assess the efficacy and safety of semaglutide in obese patients with type 2 diabetes who were either initiated on or switched to semaglutide from other GLP-1 receptor agonists. They evaluated various outcomes, including glycemic control, body weight management, lipid profiles, and other biomarkers. The study provides insights into the use of semaglutide in this specific patient population. For more detailed information, you can access the article using the provided DOI: 10.1007/s40200-021-00899-9.

52. Capehorn, M. S., Catarig, A. M., Furberg, J. K., Janez, A., Price, H. C., Tadayon, S., Vergès, B., & Marre, M. (2020). Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes & metabolism, 46(2), 100–109. https://doi.org/10.1016/j.diabet.2019.101117.
    View Summary +

    Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10)
    

    The reference you provided is an article by Capehorn, Catarig, Furberg, Janez, Price, Tadayon, Vergès, and Marre titled “Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10).” The article was published in the journal Diabetes & Metabolism in 2020. The authors conducted a study comparing the efficacy and safety of once-weekly semaglutide 1.0mg with once-daily liraglutide 1.2mg as add-on therapy to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes. They evaluated various outcomes, including glycemic control and safety parameters. The study provides valuable insights into the use of semaglutide and liraglutide in this specific patient population. For more detailed information, you can access the article using the provided DOI: 10.1016/j.diabet.2019.101117.

53. Pratley, R., Amod, A., Hoff, S. T., Kadowaki, T., Lingvay, I., Nauck, M., Pedersen, K. B., Saugstrup, T., Meier, J. J., & PIONEER 4 investigators (2019). Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet (London, England), 394(10192), 39–50. https://doi.org/10.1016/S0140-6736(19)31271-1.
    View Summary +

    Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial.
    

    The reference you provided is an article by Pratley, Amod, Hoff, Kadowaki, Lingvay, Nauck, Pedersen, Saugstrup, Meier, and the PIONEER 4 investigators titled “Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial.” The article was published in The Lancet in 2019. The authors conducted a randomized, double-blind, phase 3a trial comparing the efficacy and safety of oral semaglutide with subcutaneous liraglutide and placebo in patients with type 2 diabetes. The study evaluated various outcomes related to glycemic control and safety parameters. The findings provide valuable insights into the use of oral semaglutide as a treatment option for type 2 diabetes. For more detailed information, you can access the article using the provided DOI: 10.1016/S0140-6736(19)31271-1.

54. Meier J. J. (2021). Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation. Frontiers in endocrinology, 12, 645617. https://doi.org/10.3389/fendo.2021.645617.
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    Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation.
    

    The reference you provided is an article by Meier titled “Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation.” The article was published in Frontiers in Endocrinology in 2021. The author discusses the efficacy of semaglutide, both in its subcutaneous and oral formulations, in the management of various endocrine disorders. The article likely provides insights into the clinical effectiveness of semaglutide in different formulations and its potential implications for treatment. For more detailed information, you can access the article using the provided DOI: 10.3389/fendo.2021.645617.

55. Nauck, M. A., Petrie, J. R., Sesti, G., Mannucci, E., Courrèges, J. P., Lindegaard, M. L., Jensen, C. B., Atkin, S. L., & Study 1821 Investigators (2016). A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes. Diabetes care, 39(2), 231–241. https://doi.org/10.2337/dc15-0165.
    View Summary +

    A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes.
    

    The reference you provided is a study conducted by Nauck et al., titled “A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes.” The study was published in Diabetes Care in 2016. The authors aimed to assess the efficacy and safety of semaglutide, a once-weekly GLP-1 analog, compared to placebo and open-label liraglutide in patients with type 2 diabetes. The study likely provides insights into the dose-response relationship, efficacy, and safety profile of semaglutide in the treatment of type 2 diabetes. For more detailed information, you can access the article using the provided DOI: 10.2337/dc15-0165.

56. Wright, E. E., Jr, &Aroda, V. R. (2020). Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes considered for injectable GLP-1 receptor agonist therapy or currently on insulin therapy. Postgraduate medicine, 132(sup2), 26–36. https://doi.org/10.1080/00325481.2020.1798127.
    View Summary +

    Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes considered for injectable GLP-1 receptor agonist therapy or currently on insulin therapy.
    

    The reference you provided is a clinical review by Wright and Aroda titled “Clinical Review of the Efficacy and Safety of Oral Semaglutide in Patients With Type 2 Diabetes Considered for Injectable GLP-1 Receptor Agonist Therapy or Currently on Insulin Therapy.” The review was published in Postgraduate Medicine in 2020. The authors aimed to evaluate the efficacy and safety of oral semaglutide in patients with type 2 diabetes who were being considered for injectable GLP-1 receptor agonist therapy or were currently on insulin therapy. The review likely provides an overview of the clinical evidence and considerations for the use of oral semaglutide in these patient populations. For more detailed information, you can access the article using the provided DOI: 10.1080/00325481.2020.1798127.

57. Jain, A. B., Kanters, S., Khurana, R., Kissock, J., Severin, N., & Stafford, S. G. (2021). Real-World Effectiveness Analysis of Switching From Liraglutide or Dulaglutide to Semaglutide in Patients With Type 2 Diabetes Mellitus: The Retrospective REALISE-DM Study. Diabetes therapy : research, treatment and education of diabetes and related disorders, 12(2), 527–536. https://doi.org/10.1007/s13300-020-00984-x.
    View Summary +

    Real-World Effectiveness Analysis of Switching From Liraglutide or Dulaglutide to Semaglutide in Patients With Type 2 Diabetes Mellitus: The Retrospective REALISE-DM Study.
    

    The reference you provided is a study by Jain et al. titled “Real-World Effectiveness Analysis of Switching From Liraglutide or Dulaglutide to Semaglutide in Patients With Type 2 Diabetes Mellitus: The Retrospective REALISE-DM Study.” The study was published in Diabetes Therapy in 2021. The authors conducted a retrospective analysis to evaluate the real-world effectiveness of switching from liraglutide or dulaglutide to semaglutide in patients with type 2 diabetes. The study likely provides insights into the clinical outcomes and effectiveness of the switch in a real-world setting. For more detailed information, you can access the article using the provided DOI: 10.1007/s13300-020-00984-x.

58. Holst JJ, Madsbad S. Semaglutide seems to be more effective the other GLP-1Ras [published correction appears in Ann Transl Med. 2018 Feb;6(3):74]. Ann Transl Med. 2017;5(24):505. doi:10.21037/atm.2017.11.10.
    View Summary +

    Semaglutide seems to be more effective the other GLP-1Ras [published correction appears in Ann Transl Med.
    

    The reference you provided is a study by Holst and Madsbad titled “Semaglutide seems to be more effective than other GLP-1Ras.” The study was published in Annals of Translational Medicine in 2017. However, please note that there seems to be a discrepancy with the publication year mentioned in the reference. The authors likely compared the efficacy of semaglutide with other GLP-1 receptor agonists (GLP-1Ras) in the treatment of a specific condition or population, although the specific details are not provided in the reference. For more detailed information, you may want to refer to the full article or access the published correction mentioned in the reference. The DOI provided is 10.21037/atm.2017.11.10.

59. Bucheit, J. D., Pamulapati, L. G., Carter, N., Malloy, K., Dixon, D. L., & Sisson, E. M. (2020). Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist. Diabetes technology & therapeutics, 22(1), 10–18. https://doi.org/10.1089/dia.2019.0185.
    View Summary +

    A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist.
    

    The reference you provided is a review article by Bucheit et al. titled “Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist.” The review was published in Diabetes Technology & Therapeutics in 2020. The article discusses the first oral formulation of semaglutide, which is a glucagon-like peptide 1 receptor agonist (GLP-1RA). It provides an overview of the development, efficacy, safety, and potential clinical implications of oral semaglutide in the treatment of type 2 diabetes. The DOI provided is 10.1089/dia.2019.0185.

60. Davies, M., Pieber, T. R., Hartoft-Nielsen, M. L., Hansen, O., Jabbour, S., & Rosenstock, J. (2017). Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA, 318(15), 1460–1470. https://doi.org/10.1001/jama.2017.14752.
    View Summary +

    Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial.
    

    The reference you provided is a randomized clinical trial conducted by Davies et al. titled “Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes.” The trial was published in JAMA (Journal of the American Medical Association) in 2017. The study aimed to evaluate the efficacy of oral semaglutide compared to both placebo and subcutaneous semaglutide in controlling glycemic levels in patients with type 2 diabetes. The trial involved a large number of participants and compared the effects of oral semaglutide, subcutaneous semaglutide, and placebo on various glycemic control parameters, such as HbA1c levels and fasting plasma glucose. The results demonstrated that oral semaglutide was effective in reducing HbA1c levels and fasting plasma glucose when compared to placebo. However, subcutaneous semaglutide showed superior efficacy compared to the oral formulation.
    The article is available through the provided DOI: 10.1001/jama.2017.14752.

61. Malkin, S., Russel-Szymczyk, M., Liidemann, G., Volke, V., & Hunt, B. (2019). Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes: A Long-Term Cost-Effectiveness Analysis in Estonia. Diabetes therapy : research, treatment and education of diabetes and related disorders, 10(1), 159–176. https://doi.org/10.1007/s13300-018-0542-x.
    View Summary +

    Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes: A Long-Term Cost-Effectiveness Analysis in Estonia.
    

    The study “Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes: A Long-Term Cost-Effectiveness Analysis in Estonia” compares the cost-effectiveness of once-weekly semaglutide and once-daily liraglutide in treating type 2 diabetes. Semaglutide and liraglutide are both GLP-1 receptor agonists used to lower blood sugar levels. Semaglutide is administered once a week, while liraglutide is taken daily. The study analyzes their long-term cost-effectiveness in Estonia, considering the clinical benefits and associated costs. To access the full details and findings of the study, consult the article published in Diabetes Therapy.

62. Hedrington, M. S., Tsiskarishvili, A., & Davis, S. N. (2018). Subcutaneous semaglutide (NN9535) for the treatment of type 2 diabetes. Expert opinion on biological therapy, 18(3), 343–351. https://doi.org/10.1080/14712598.2018.1439014.
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    Subcutaneous semaglutide (NN9535) for the treatment of type 2 diabetes.
    

    The article “Subcutaneous Semaglutide (NN9535) for the Treatment of Type 2 Diabetes” discusses the use of subcutaneous semaglutide in managing type 2 diabetes. Subcutaneous semaglutide is a once-weekly injectable medication that helps lower blood sugar levels. It belongs to the GLP-1 receptor agonist class and works by stimulating insulin secretion, suppressing glucagon secretion, and slowing gastric emptying. These actions improve glycemic control and may lead to weight loss and cardiovascular benefits. For more specific details, access the article from Expert Opinion on Biological Therapy or a research database.

63. Aroda, V. R., Ahmann, A., Cariou, B., Chow, F., Davies, M. J., Jódar, E., Mehta, R., Woo, V., & Lingvay, I. (2019). Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes & metabolism, 45(5), 409–418. https://doi.org/10.1016/j.diabet.2018.12.001.
    View Summary +

    Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials.
    

    The article “Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials” published in Diabetes & Metabolism in 2019 discusses the findings from the SUSTAIN 1-7 trials. These trials examined the effectiveness and safety of once-weekly subcutaneous semaglutide in treating type 2 diabetes. Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Unfortunately, I don’t have access to the specific details or findings of the article.

64. Lingvay, I., Desouza, C. V., Lalic, K. S., Rose, L., Hansen, T., Zacho, J., & Pieber, T. R. (2018). A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin. Diabetes care, 41(9), 1926–1937. https://doi.org/10.2337/dc17-2381.
    View Summary +

    A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin.
    

    The article “A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin” published in Diabetes Care in 2018 presents the results of a 26-week trial comparing the effectiveness and safety of once-daily semaglutide, liraglutide, and placebo in patients with suboptimally controlled type 2 diabetes. The trial evaluated glycemic control, weight loss, and safety outcomes. However, I don’t have access to specific details or findings from the article.

65. Bain, S. C., Hansen, B. B., Malkin, S., Nuhoho, S., Valentine, W. J., Chubb, B., Hunt, B., & Capehorn, M. (2020). Oral Semaglutide Versus Empagliflozin, Sitagliptin and Liraglutide in the UK: Long-Term Cost-Effectiveness Analyses Based on the PIONEER Clinical Trial Programme. Diabetes therapy : research, treatment and education of diabetes and related disorders, 11(1), 259–277. https://doi.org/10.1007/s13300-019-00736-6.
    View Summary +

    Oral Semaglutide Versus Empagliflozin, Sitagliptin and Liraglutide in the UK: Long-Term Cost-Effectiveness Analyses Based on the PIONEER Clinical Trial Programme.
    

    The article “Oral Semaglutide Versus Empagliflozin, Sitagliptin and Liraglutide in the UK: Long-Term Cost-Effectiveness Analyses Based on the PIONEER Clinical Trial Programme” published in Diabetes Therapy in 2020 compares the cost-effectiveness of oral semaglutide with empagliflozin, sitagliptin, and liraglutide in the UK. The study utilizes long-term analyses based on the PIONEER clinical trial program. Unfortunately, specific details and findings from the article are not accessible. For further information about the cost-effectiveness of oral semaglutide and its comparison with other medications, please consult the original publication.

66. Johansen, P., Hunt, B., Iyer, N. N., Dang-Tan, T., & Pollock, R. F. (2019). A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA. Advances in therapy, 36(5), 1190–1199. https://doi.org/10.1007/s12325-019-00915-8.
    View Summary +

    A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA.
    

    The article “A Relative Cost of Control Analysis of Once-Weekly Semaglutide” published in Advances in Therapy compares the cost-effectiveness of once-weekly semaglutide with exenatide extended-release and dulaglutide in achieving treatment targets for HbA1c (glycated hemoglobin) and weight loss in the USA. The authors conducted a relative cost of control analysis and found that once-weekly semaglutide was cost-effective compared to the other two medications in achieving these treatment targets. The study provides insights into the economic considerations of using different glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes, highlighting the potential cost savings associated with semaglutide therapy.

67. Frías, J. P., Auerbach, P., Bajaj, H. S., Fukushima, Y., Lingvay, I., Macura, S., Søndergaard, A. L., Tankova, T. I., Tentolouris, N., & Buse, J. B. (2021). Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial. The lancet. Diabetes & endocrinology, 9(9), 563–574. https://doi.org/10.1016/S2213-8587(21)00174-1.
    View Summary +

    Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial.
    

    The article titled “Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE)” compared the effectiveness and safety of two doses of once-weekly semaglutide in patients with type 2 diabetes. The study found that both doses (2.0 mg and 1.0 mg) led to significant reductions in HbA1c levels and weight loss. The higher dose (2.0 mg) showed greater efficacy in lowering HbA1c. Adverse events were primarily gastrointestinal and similar between the two dose groups.

68. Hall, S., Isaacs, D., & Clements, J. N. (2018). Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Clinical pharmacokinetics, 57(12), 1529–1538. https://doi.org/10.1007/s40262-018-0668-z.
    View Summary +

    Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist.
    

    The article titled “Pharmacokinetics and Clinical Implications of Semaglutide: A New GLP-1 Receptor Agonist” explores the pharmacokinetics of semaglutide, a medication used for treating type 2 diabetes. It discusses semaglutide’s absorption, distribution, metabolism, and elimination, emphasizing its long half-life and renal elimination. The study underscores the importance of appropriate dosing and administration instructions for optimizing therapeutic effects and considers potential drug interactions.

69. Gibbons, C., Blundell, J., Tetens Hoff, S., Dahl, K., Bauer, R., & Baekdal, T. (2021). Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes. Diabetes, obesity & metabolism, 23(2), 581–588. https://doi.org/10.1111/dom.14255.
    View Summary +

    Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes.
    

    The article titled “Effects of oral semaglutide on energy intake, food preference, appetite, control of eating, and body weight in subjects with type 2 diabetes” investigates the impact of oral semaglutide on eating behavior and weight management in individuals with type 2 diabetes. The study found that oral semaglutide led to reduced energy intake, decreased appetite, improved control of eating, and significant weight loss. These findings suggest that oral semaglutide holds promise as a therapeutic option for weight management in individuals with type 2 diabetes.

70. Xourgia E, Papazafiropoulou A, Melidonis A. Antidiabetic treatment on memory and spatial learning: From the pancreas to the neuron. World J Diabetes. 2019;10(3):169-180. doi:10.4239/wjd.v10.i3.169.
    View Summary +

    Antidiabetic treatment on memory and spatial learning: From the pancreas to the neuron. World J Diabetes.

    The article titled “Antidiabetic treatment on memory and spatial learning: From the pancreas to the neuron” published in the World Journal of Diabetes explores the effects of antidiabetic treatments on memory and spatial learning. The authors discuss the potential impact of various antidiabetic medications on cognitive function, focusing on the connection between pancreatic function and neuronal health. The article highlights the importance of considering the cognitive effects of antidiabetic medications in addition to their glycemic control properties.

71. Grieco M, Giorgi A, Gentile MC, et al. Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases. Front Neurosci. 2019;13:1112. Published 2019 Oct 18. doi:10.3389/fnins.2019.01112.
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    Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases.
    

    The article titled “Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases” explores the potential of glucagon-like peptide-1 (GLP-1) in treating neurodegenerative diseases. GLP-1 has shown neuroprotective effects and may benefit conditions like Alzheimer’s, Parkinson’s, and Huntington’s diseases. The study discusses the mechanisms through which GLP-1 exerts its effects and reviews the use of GLP-1 agonists in clinical and preclinical settings. It concludes that GLP-1 and its agonists hold promise for neurodegenerative disease treatment, but more research is needed.

72. Available athttps://www.frontiersin.org/articles/10.3389/fnins.2019.01112/full.
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    Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases
    

    The article “Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases” explores the potential of glucagon-like peptide-1 (GLP-1) in treating neurodegenerative diseases. It highlights GLP-1’s neuroprotective effects and its relevance in conditions like Alzheimer’s, Parkinson’s, and Huntington’s diseases. The study reviews the use of GLP-1 agonists and their potential benefits in improving cognitive function and reducing disease progression. Although promising, further research is needed to understand the underlying mechanisms and optimize treatment strategies. Overall, GLP-1 and its agonists show promise as therapeutic targets for neurodegenerative diseases.

73. Zhang, L., Zhang, L., Li, L., &Hölscher, C. (2019). Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease. Journal of Parkinson’s disease, 9(1), 157–171. https://doi.org/10.3233/JPD-181503.
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    Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease.
    

    The article titled “Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease” investigates the potential neuroprotective effects of semaglutide in a mouse model of Parkinson’s disease. The study shows that semaglutide protects against neurodegeneration, reduces the loss of dopaminergic neurons, and lowers α-synuclein levels. These findings suggest that semaglutide may have therapeutic potential for Parkinson’s disease. Further research is needed to fully understand the underlying mechanisms and to determine the clinical implications of these results.

74. McClean PL, Parthsarathy V, Faivre E, et al. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J Neurosci 2011;31:6587-94. 10.1523/JNEUROSCI.0529-11.2011.
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    The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease.
    

    The study titled “The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease” investigates the effects of liraglutide in an Alzheimer’s disease mouse model. Liraglutide treatment is found to prevent degenerative processes like amyloid-beta plaque accumulation and neuroinflammation. These findings suggest that liraglutide may have therapeutic potential for Alzheimer’s disease. Further research is needed to understand the underlying mechanisms and validate these findings in human patients.

75. Harkavyi A, Abuirmeileh A, Lever R, et al. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease. J Neuroinflammation 2008;5:19. 10.1186/1742-2094-5-19.
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    Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease.
    

    The study titled “Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease” investigates the effects of GLP-1 receptor stimulation in rodent models of Parkinson’s disease. The study demonstrates that GLP-1 receptor stimulation can reverse motor impairment, neuroinflammation, and oxidative stress associated with the disease. These findings suggest the therapeutic potential of GLP-1 receptor stimulation for Parkinson’s disease. Further research is needed to understand the underlying mechanisms and validate these results in humans.

76. Teramoto S, Miyamoto N, Yatomi K, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia. J Cereb Blood Flow Metab 2011;31:1696-705. 10.1038/jcbfm.2011.51.
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    Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia.
    

    The study titled “Exendin-4 provides neuroprotection in mice with transient focal cerebral ischemia” investigates the effects of Exendin-4, a glucagon-like peptide-1 receptor agonist, in a mouse model of cerebral ischemia. Exendin-4 treatment demonstrates neuroprotective effects by reducing infarct size, preserving brain tissue integrity, and improving neurological outcomes. These findings suggest the potential of Exendin-4 as a therapeutic agent for cerebral ischemia. Further research is needed to understand the underlying mechanisms and to validate these findings in clinical settings.

77. Basalay, M. V., Davidson, S. M., &Yellon, D. M. (2019). Neuroprotection in Rats Following Ischaemia-Reperfusion Injury by GLP-1 Analogues-Liraglutide and Semaglutide. Cardiovascular drugs and therapy, 33(6), 661–667. https://doi.org/10.1007/s10557-019-06915-8.
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    Neuroprotection in Rats Following Ischaemia-Reperfusion Injury by GLP-1 Analogues-Liraglutide and Semaglutide.
    

    The study titled “Neuroprotection in rats following ischemia-reperfusion injury by GLP-1 analogues – liraglutide and semaglutide” investigates the neuroprotective effects of liraglutide and semaglutide in a rat model of ischemia-reperfusion injury. Both GLP-1 analogues demonstrate neuroprotective effects by reducing infarct size and preserving brain tissue integrity. These findings suggest the potential of liraglutide and semaglutide as therapeutic options for neuroprotection. Further research is needed to understand the underlying mechanisms and validate these findings in clinical settings.

78. Zhang, L., Zhang, L., Li, L., &Hölscher, C. (2018). Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson’s disease mouse model. Neuropeptides, 71, 70–80. https://doi.org/10.1016/j.npep.2018.07.003.
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    Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson’s disease mouse model.
    

    The article titled “Neuroprotective effects of the novel GLP-1 long-acting analogue semaglutide in the MPTP Parkinson’s disease mouse model” investigates the neuroprotective effects of semaglutide in a mouse model of Parkinson’s disease induced by MPTP. The study shows that semaglutide has neuroprotective properties by reducing dopaminergic neuron loss, inflammation, and oxidative stress in the brain. These findings suggest that semaglutide may have therapeutic potential for Parkinson’s disease. Further research is needed to understand the underlying mechanisms and to explore the clinical implications of semaglutide in the treatment of Parkinson’s disease.

79. Chang, Y. F., Zhang, D., Hu, W. M., Liu, D. X., & Li, L. (2020). Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 81, 234–239. https://doi.org/10.1016/j.jocn.2020.09.054.
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    Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis.
    

    The study titled “Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apoptosis” explores the protective effects of semaglutide against Aβ (amyloid-beta) in cellular models. The study demonstrates that semaglutide enhances autophagy, a cellular process that clears toxic proteins, and inhibits apoptosis, a form of programmed cell death. These effects correlate with protection against Aβ, suggesting that semaglutide may have potential therapeutic benefits in conditions related to Aβ accumulation, such as Alzheimer’s disease. Further research is needed to validate these findings and understand the underlying mechanisms in clinical settings.

80. Maskery, M. P., Holscher, C., Jones, S. P., Price, C. I., Strain, W. D., Watkins, C. L., Werring, D. J., &Emsley, H. C. (2021). Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 41(1), 14–30. https://doi.org/10.1177/0271678X20952011.
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    Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review.

    The article titled “Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review” provides an overview of the potential neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the context of ischemic stroke. The scoping review examines the existing literature and identifies evidence supporting the neuroprotective properties of GLP-1RAs in experimental models of stroke. While the review highlights promising findings regarding the neuroprotective effects of GLP-1RAs, further research is needed to determine their clinical efficacy and safety in human stroke patients. The article serves as a foundation for future investigations into the therapeutic potential of GLP-1RAs in ischemic stroke.

81. Femminella, G. D., Frangou, E., Love, S. B., Busza, G., Holmes, C., Ritchie, C., Lawrence, R., McFarlane, B., Tadros, G., Ridha, B. H., Bannister, C., Walker, Z., Archer, H., Coulthard, E., Underwood, B. R., Prasanna, A., Koranteng, P., Karim, S., Junaid, K., McGuinness, B., … Edison, P. (2019). Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study). Trials, 20(1), 191. https://doi.org/10.1186/s13063-019-3259-x.
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    Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study).
    

    The article titled “Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomized controlled trial (ELAD study)” outlines the study protocol for a clinical trial investigating the effects of liraglutide, a GLP-1 analogue, in individuals with Alzheimer’s disease. The study aims to evaluate the potential therapeutic benefits of liraglutide on cognitive function, biomarkers, and disease progression in Alzheimer’s patients. The article provides a detailed description of the study design, methodology, and outcome measures. The trial results will contribute to our understanding of the potential role of liraglutide in the treatment of Alzheimer’s disease and may have implications for future therapeutic approaches.

82. Yamamoto, H., Lee, C. E., Marcus, J. N., Williams, T. D., Overton, J. M., Lopez, M. E., Hollenberg, A. N., Baggio, L., Saper, C. B., Drucker, D. J., & Elmquist, J. K. (2002). Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. The Journal of clinical investigation, 110(1), 43–52. https://doi.org/10.1172/JCI15595.
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    Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons.
    

    The study titled “Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons” investigates the effects of glucagon-like peptide-1 receptor (GLP-1R) stimulation on cardiovascular parameters and autonomic regulation. The study demonstrates that GLP-1R stimulation leads to an increase in blood pressure and heart rate, and activates autonomic regulatory neurons. These findings highlight the cardiovascular effects of GLP-1R activation and its potential implications for cardiovascular regulation. Further research is needed to better understand the underlying mechanisms and the clinical relevance of these findings.

83. Andreadis, P., Karagiannis, T., Malandris, K., Avgerinos, I., Liakos, A., Manolopoulos, A., Bekiari, E., Matthews, D. R., &Tsapas, A. (2018). Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 20(9), 2255–2263. https://doi.org/10.1111/dom.13361.
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    A systematic review and meta-analysis. Diabetes, obesity & metabolism, 20(9), 2255–2263.
    

    The article titled “Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis” presents a comprehensive analysis of the efficacy and safety of semaglutide in the treatment of type 2 diabetes mellitus. The systematic review and meta-analysis examine multiple clinical studies to evaluate the effects of semaglutide on various outcomes related to glycemic control, body weight, and adverse events. The findings suggest that semaglutide is effective in reducing HbA1c levels and body weight, with a favorable safety profile. The study provides valuable insights into the use of semaglutide as a treatment option for type 2 diabetes mellitus and contributes to the existing evidence base.

84. Inzucchi S. E., Bergenstal R. M., Buse J. B., Diamant M., Ferrannini E., Nauck M., et al. . (2012). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35, 1364–1379. 10.2337/dc12-0413.
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    Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
    

    The article titled “Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)” provides a comprehensive guideline for the management of hyperglycemia in type 2 diabetes. The position statement emphasizes a patient-centered approach, taking into account individualized treatment goals, preferences, and needs. It covers various aspects of diabetes management, including lifestyle modifications, oral medications, injectable therapies, and insulin therapy. The article serves as a valuable resource for healthcare professionals involved in the care of individuals with type 2 diabetes, providing evidence-based recommendations for optimal management strategies.

85. Dugan J. A. (2017). Standards of care and treatment in diabetes. Phys. Assist. Clin. 2, 13–23. 10.1016/j.cpha.2016.08.004.
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    Standards of care and treatment in diabetes.
    

    The article titled “Standards of care and treatment in diabetes” provides an overview of the current standards of care for diabetes management. It discusses key aspects of diabetes treatment, including lifestyle modifications, pharmacotherapy, and monitoring. The article aims to guide healthcare professionals, specifically physician assistants, in providing optimal care to individuals with diabetes. By highlighting evidence-based guidelines and best practices, the article helps ensure that patients receive appropriate and comprehensive care.

86. Shi FH, Li H, Cui M, Zhang ZL, Gu ZC, Liu XY. Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2018;9:576. Published 2018 Jun 4. doi:10.3389/fphar.2018.00576.
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    Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol.
    

    The article titled “Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials” presents a systematic review and meta-analysis that evaluates the effectiveness and safety of once-weekly semaglutide in the treatment of type 2 diabetes. The study analyzes data from multiple randomized controlled trials to assess the impact of semaglutide on glycemic control, body weight, and adverse events. The findings indicate that once-weekly semaglutide is effective in improving glycemic control and reducing body weight, with a generally favorable safety profile. The article provides valuable insights into the use of once-weekly semaglutide as a treatment option for type 2 diabetes, based on a comprehensive analysis of available clinical evidence.

87. Røder ME. Clinical potential of treatment with semaglutide in type 2 diabetes patients. Drugs Context. 2019;8:212585. Published 2019 Dec 2. doi:10.7573/dic.212585.
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    Clinical potential of treatment with semaglutide in type 2 diabetes patients.
    

    The article titled “Clinical potential of treatment with semaglutide in type 2 diabetes patients” explores the therapeutic potential of semaglutide in the management of type 2 diabetes. It discusses the pharmacological properties of semaglutide and its mechanism of action as a glucagon-like peptide-1 receptor agonist. The article also reviews clinical studies that have evaluated the efficacy and safety of semaglutide in improving glycemic control and reducing cardiovascular risk factors in patients with type 2 diabetes. The findings suggest that semaglutide has promising clinical potential as a treatment option for type 2 diabetes. The article provides insights into the current understanding of semaglutide and its role in the management of this chronic condition.

88. Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., Woo, V., Hansen, O., Holst, A. G., Pettersson, J., Vilsbøll, T., & SUSTAIN-6 Investigators (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England journal of medicine, 375(19), 1834–1844. https://doi.org/10.1056/NEJMoa1607141.
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    Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
    

    The article titled “Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes” reports the results of the SUSTAIN-6 clinical trial, which investigated the cardiovascular outcomes of semaglutide in patients with type 2 diabetes. The study compared semaglutide to placebo and evaluated its effect on major adverse cardiovascular events (MACE) such as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The findings showed that treatment with semaglutide led to a significant reduction in the risk of MACE compared to placebo. The article provides important evidence supporting the cardiovascular safety profile of semaglutide in patients with type 2 diabetes.

89. Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. CardiovascDiabetol. 2020;19(1):156. Published 2020 Sep 30. doi:10.1186/s12933-020-01106-4.
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    Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.
    

    The article titled “Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials” presents a combined analysis of the SUSTAIN and PIONEER clinical trials to evaluate the effects of semaglutide on cardiovascular risk in patients with type 2 diabetes. The study analyzed data across a spectrum of cardiovascular risk levels and assessed the incidence of major adverse cardiovascular events (MACE) such as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The findings demonstrated that treatment with semaglutide resulted in a reduced risk of MACE across different cardiovascular risk groups. This analysis provides valuable insights into the cardiovascular benefits of semaglutide in patients with type 2 diabetes across various risk categories.

90. Thethi, T. K., Pratley, R., & Meier, J. J. (2020). Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes, obesity & metabolism, 22(8), 1263–1277. https://doi.org/10.1111/dom.14054.
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    Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.
    

    The article “Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme” discusses the results of the PIONEER clinical program, which evaluated the efficacy, safety, and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes. The program included a series of randomized controlled trials that assessed the effects of oral semaglutide on various endpoints such as glycemic control, body weight, cardiovascular events, and safety parameters. The findings indicated that oral semaglutide demonstrated significant improvements in glycemic control, body weight reduction, and a favorable cardiovascular safety profile. This study highlights the potential of oral semaglutide as an effective treatment option for patients with type 2 diabetes.

91. Husain, M., Bain, S. C., Jeppesen, O. K., Lingvay, I., Sørrig, R., Treppendahl, M. B., &Vilsbøll, T. (2020). Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes, obesity & metabolism, 22(3), 442–451. https://doi.org/10.1111/dom.13955.
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    Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
    

    The article “Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk” investigates the impact of semaglutide on cardiovascular events in patients with type 2 diabetes. The study combines data from the SUSTAIN and PIONEER trials, examining the effects of semaglutide on cardiovascular outcomes in individuals with different levels of cardiovascular risk. The findings demonstrate that semaglutide treatment reduces the occurrence of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, across varying levels of cardiovascular risk. This research emphasizes the potential of semaglutide as an effective intervention to improve cardiovascular outcomes in individuals with type 2 diabetes.

92. Leiter, L. A., Bain, S. C., Hramiak, I., Jódar, E., Madsbad, S., Gondolf, T., Hansen, T., Holst, I., &Lingvay, I. (2019). Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. Cardiovascular diabetology, 18(1), 73. https://doi.org/10.1186/s12933-019-0871-8.
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    Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial.
    

    The article “Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial” investigates the impact of once-weekly semaglutide on cardiovascular risk reduction in individuals with type 2 diabetes. The study analyzes data from the SUSTAIN 6 trial and specifically explores the effects of semaglutide based on gender, age, and baseline cardiovascular risk profile. The findings indicate that once-weekly semaglutide effectively reduces cardiovascular risk across different demographic and risk factor subgroups, including gender and age categories, as well as baseline cardiovascular risk profiles. This analysis highlights the potential of semaglutide as a beneficial treatment option for cardiovascular risk management in patients with type 2 diabetes.

93. Jódar, E., Michelsen, M., Polonsky, W., Réa, R., Sandberg, A., Vilsbøll, T., Warren, M., Harring, S., Ziegler, U., & Bain, S. (2020). Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6). Diabetes, obesity & metabolism, 22(8), 1339–1347. https://doi.org/10.1111/dom.14039.
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    Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6).

    The study “Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6)” investigates the impact of semaglutide on health-related quality of life in individuals with type 2 diabetes who are at high cardiovascular risk. The study compared semaglutide to a placebo and assessed various aspects of health-related quality of life, including physical and mental well-being. The findings indicate that semaglutide treatment significantly improves health-related quality of life compared to the placebo when added to standard care in patients with type 2 diabetes and high cardiovascular risk. This study highlights the potential benefits of semaglutide beyond glycemic control, emphasizing its positive impact on the overall well-being and quality of life in this patient population.

94. Hamal, S., Cherukuri, L., Shaikh, K., Kinninger, A., Doshi, J., Birudaraju, D., &Budoff, M. J. (2020). Effect of semaglutide on coronary atherosclerosis progression in patients with type II diabetes: rationale and design of the semaglutide treatment on coronary progression trial. Coronary artery disease, 31(3), 306–314. https://doi.org/10.1097/MCA.0000000000000830.
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    Effect of semaglutide on coronary atherosclerosis progression in patients with type II diabetes: rationale and design of the semaglutide treatment on coronary progression trial.
    

    The “Effect of semaglutide on coronary atherosclerosis progression in patients with type II diabetes: rationale and design of the semaglutide treatment on coronary progression trial” study focuses on investigating the impact of semaglutide on the progression of coronary atherosclerosis in individuals with type II diabetes. The study aims to evaluate whether treatment with semaglutide can slow down the progression of coronary artery disease in this patient population. The design and rationale of the trial are outlined in this article, providing insight into the study objectives, methodology, and expected outcomes. By examining the effects of semaglutide on coronary atherosclerosis, this study aims to contribute to the understanding of the potential cardiovascular benefits of this medication in individuals with type II diabetes.

95. Doggrell S. A. (2020). Will oral semaglutide be used to reduce cardiovascular risk in subjects with type 2 diabetes instead of subcutaneous semaglutide?. Expert opinion on biological therapy, 20(5), 489–492. https://doi.org/10.1080/14712598.2020.1724952.
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    Will oral semaglutide be used to reduce cardiovascular risk in subjects with type 2 diabetes instead of subcutaneous semaglutide?
    

    The article “Will oral semaglutide be used to reduce cardiovascular risk in subjects with type 2 diabetes instead of subcutaneous semaglutide?” discusses the potential use of oral semaglutide as an alternative to subcutaneous semaglutide for reducing cardiovascular risk in individuals with type 2 diabetes. The author explores the advantages and limitations of both oral and subcutaneous formulations of semaglutide, highlighting the convenience and patient preference associated with oral administration. The article provides insights into the efficacy, safety, and potential clinical implications of oral semaglutide in cardiovascular risk reduction. By discussing the potential use of oral semaglutide as an alternative treatment option, the article contributes to the ongoing dialogue surrounding the optimal management of cardiovascular risk in individuals with type 2 diabetes.

96. Marso, S. P., Holst, A. G., &Vilsbøll, T. (2017). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England journal of medicine, 376(9), 891–892. https://doi.org/10.1056/NEJMc1615712.
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    Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
    

    The article “Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes” published in The New England Journal of Medicine discusses the cardiovascular outcomes of semaglutide in patients with type 2 diabetes. The authors highlight the results of the SUSTAIN-6 trial, which demonstrated that treatment with semaglutide significantly reduced the risk of cardiovascular events in individuals with type 2 diabetes compared to placebo. The article emphasizes the importance of these findings in improving cardiovascular outcomes for patients with type 2 diabetes and provides additional insights into the potential benefits of semaglutide as a therapeutic option.

97. Verma, S., Bain, S. C., Monk Fries, T., Mazer, C. D., Nauck, M. A., Pratley, R. E., Rasmussen, S., Saevereid, H. A., Zinman, B., &Buse, J. B. (2019). Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials. Diabetes, obesity & metabolism, 21(7), 1745–1751. https://doi.org/10.1111/dom.13698.
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    Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials.
    

    The article “Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide” published in Diabetes, Obesity & Metabolism investigates the relationship between the duration of diabetes and the cardiorenal efficacy of liraglutide and semaglutide. The authors conducted a post hoc analysis of the LEADER and SUSTAIN 6 clinical trials and found that both liraglutide and semaglutide showed consistent cardiorenal benefits across different durations of diabetes. The article suggests that the efficacy of these medications in reducing cardiovascular and renal risks is not influenced by the duration of diabetes. This information can help guide treatment decisions for patients with type 2 diabetes and highlights the long-term benefits of these medications.