Semaglutide

Overall Health Benefits of Semaglutide

• Promotes fat loss [1-33]
• Fights type 2 diabetes [34-57]
• Prevents cognitive decline [58-69]
• Lowers blood pressure [4] [70-75]
• Lowers the risk of cardiovascular disease [76-83]

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

Promotes Fat Loss

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. [1]
2. In obese people, administration of semaglutide once a weekvia subcutaneous injects produced superior weight loss compared to placebo. [2]
3. In obese patients with type 2 diabetes, administration of semaglutide demonstrated huge weight loss efficacy. [3]
4. In overweight and obese adults, treatment with 2.4 mg semaglutide once weekly resulted in continued weight loss for the following 48 weeks. [4]
5. A study showed that combination of physical activity and dietary supplementation of semaglutide resulted in greater weight loss. [5]
6. In obese, overweight, and type-2 diabetic adults, administration of 2.4 mg semaglutide once a week decreased bodyweight. [6]
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. [7]
8. A study showed that semaglutide induced weight loss in subjects with type 2 diabetes regardless of baseline body mass index (BMI). [8]
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. [9]
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. [10]
11. A study showed that semaglutide administration once a day produced weight loss by reducing HbA_1c, a measure of blood sugar. [11]
12. A study showed thatintake of semaglutideonce a week improved blood sugar control and reduced body weight in patients with type-2 diabetes. [12]
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. [13-15]
14. Studies suggest that semaglutide is superior to other weight loss medications with regards to efficacy and cost-effectiveness. [16-24]
15. In overweight and obese adults, once per week administration of semaglutide resulted in significant and sustained weight reduction. [25]
16. In obese patients, semaglutide was well-tolerated and induced significant weight loss. [26]
17. A review of studies showed that once weekly semaglutide was successful in inducing significant weight loss. [27]
18. A study showed that oral semaglutide was effective in body weight reduction. [28]
19. A review of studies showed that semaglutide demonstrated superior efficacy in obesity compared to other anti-diabetic drugs. [29]
20. In obese or overweight adults, semaglutide administration resulted in significant weight loss. [30]
21. In obese or overweight adults, semaglutide administration in addition to weight management program was effective in inducing weight reduction. [31]
22. A study showed that semaglutide offered the greatest weight-reducing effect among any obesity medication. [32]
23. In obese or overweight adults, once-weekly administration of semaglutide resulted in significant weight loss. [33]

Fights Type 2 Diabetes

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

1. In patients with type 2 diabetes, semaglutideadministration once a week resulted in decreased blood sugar levels. [34]
2. A study showed that oral administration of semaglutide in type 2 diabetics reduced glycosylatedhemoglobin, which is chemically linked to sugar. [35]
3. In patients with type 2 diabetes, oral semaglutide improved blood sugar control. [36]
4. A study showed that oral semaglutide can effectively and safely reduce blood sugar, body weight and systolic blood pressure. [37]
5. In adults with type 2 diabetes,clinical trials showed the efficacy of semaglutide in reducing blood sugar levels. [38]
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. [39]
7. A review of studies showed that oral semaglutide administration is effective in treating type 2 diabeteswithout increasing the incidence of major adverse effects. [40]
8. In Japanese patients with type 2 diabetes, semaglutide was efficacious in reducing blood sugar levels and was well-tolerated. [41]
9. In type 2 diabetic patients, semaglutide was shown to be highly effective in controlling blood sugar levels compared with other diabetic medications. [42-57]

Prevents Cognitive Decline

Evidence shows that semaglutide has the capacity to prevent age-related cognitive decline:

1. In mice models of Parkinson’s disease (PD), semaglutide produced significant neuroprotective and cognitive-enhancing effects. [58]
2. In PD mouse models, semaglutide attenuated the effects of the disease by protecting the brain neurons against injury. [59]
3. In animal models, semaglutide protected against diabetes and obesity-related cognitive deficits. [60]
4. In a mouse model of PD, semaglutide exerted its neuroprotective effects by reducing motor impairments. [61]
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. [62-65]
6. In non-diabetic rat model of acute ischemic stroke, semaglutide reduced infarct size (dead brain tissue) by up to 90%. [66]
7. In a Parkinson’s disease mouse model, semaglutide alleviated the inflammation response, reduced lipid peroxidation (oxidative stress), and inhibited programmed cell death. [67-69]

Lowers Blood Pressure

Semaglutide has also been shown to have blood pressure-lowering effects:

1. A review of multiple studies found that semaglutide lowered blood pressure compared to placebo. [70]
2. In patients with type 2 diabetes, oral semaglutide effectively and safely reduced systolic blood pressure. [71]
3. 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. [72-73]
4. A study found that both doses of semaglutide (0.5 and 1.0 mg) were associated with reductions in systolic blood pressure. [74-75]
5. In overweight and obese adults, subcutaneous injection of semaglutide reduced systolic blood pressure after 20 weeks. [4]

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. [76]
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. [77-78]
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. [79]
4. A study found that semaglutide decreased the risk of atherosclerosis (plaque formation within the heart arteries) and other cardiovascular events in diabetic patients. [80-83]

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 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. [6]
2. 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. [4]
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. [7]
4. 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. [43]
5. In subjects with inadequately controlled type 2 diabetes, semaglutide-induced weight loss was consistently greater than liraglutide, regardless of baseline BMI. [9]
6. A study reported that semaglutide demonstrated superior HbA1c and body weight reductions compared with liraglutide 1.2 mg. [15]
7. 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. [84]
8. 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. [45]
9. Several studies showed that both oral and injectable semaglutide demonstrated greater efficacy than liraglutide in reducing body weight and blood sugar levels. [43-57]

References:

1. 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
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Available from https://care.diabetesjournals.org/content/41/9/1926.figures-only.
12. 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.
13. Available from https://insight.jci.org/articles/view/133429.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. 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.
52. 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.
53. 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.
54. 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.
55. 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.
56. 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.
57. 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.
58. 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.
59. 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.
60. Available athttps://www.frontiersin.org/articles/10.3389/fnins.2019.01112/full.
61. 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.
62. 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.
63. 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.
64. 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.
65. 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.
66. 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.
67. 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.
68. 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.
69. 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.
70. 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.
71. 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.
72. Dugan J. A. (2017). Standards of care and treatment in diabetes. Phys. Assist. Clin. 2, 13–23. 10.1016/j.cpha.2016.08.004.
73. 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.
74. 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.
75. 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.
76. 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.
77. 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.
78. 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.
79. 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.
80. 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.
81. 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.
82. 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.
83. 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.
84. 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.