Tirzepatide

Overall Health Benefits of Tirzepatide

• Lowers blood sugar levels [1-26]
• Promotes weight loss [1-4, 7-8, 13-15, 18, 27-30]
• Lowers the risk of heart disease [31-35]
• Improves liver health [36-40]

What is Tirzepatide?

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA). It is an experimental drug proposed to help treat medical conditions such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease. This compound is administered into the subcutaneous tissue, which is the fatty area just beneath the skin. In 2021, tirzepatide has completed phase 3 trials.

How Tirzepatide Works?

Tirzepatide works by activating both the GLP-1 and GIP receptors in your body. This triggers the release of insulin from your pancreas that blocks glucagon, a hormone that increases blood sugar levels. As a result, your blood sugar levels can be controlled effectively, especially after a meal. In addition, tirzepatide affects certain chemicals in the brain which in turn decreases food intake, increases energy expenditure, and prevents ectopic fat deposition (abnormal fat accumulation in body parts that normally contains small amounts of fat). These effects result in significant weight reductions.

Chemical Structure of Tirzepatide

Research on Tirzepatide

A. Lowers Blood Sugar Levels

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA). By acting on these receptors, it produces synergistic effects like increased insulin production and release. This makes tirzepatide more effective than strict GLP-1 agonists that are already approved for the treatment of type 2 diabetes.

By increasing insulin secretion and blocking glucagon, tirzepatide can help lower blood sugar levels. Research indicates that this effect is beneficial in patients with type 2 diabetes (T2D):

1. In T2D patients, tirzepatide administration resulted in reduced body weight and improved glycemic (blood sugar) control. [1]
2. A study showed that tirzepatide produced potent glucose and weight-lowering effects in obese diabetic patients. [2]
3. In diabetic patients, tirzepatide was shown to be the most effective treatment for T2D because of its benefits on glucose and weight control. [3]
4. In T2D patients, tirzepatide induced greater reductions in overall blood sugar levels and body weight and was associated with a lower risk of hypoglycemia (abnormally low blood sugar levels). [4]
5. In T2D patients, tirzepatide was safe and effective in improving glycemic control and body weight. [5]
6. In T2D patients, once-weekly administration of tirzepatide resulted in a significant reduction in overall blood sugar levels. [6]
7. In T2D patients, tirzepatide improved markers of insulin sensitivity and beta-cell function. [7]
8. In adult T2D patients, tirzepatide showed significant improvements in glycemic control and body weight without increased risk of hypoglycemia. [8]
9. In patients with T2D and elevated cardiovascular risk, tirzepatide offered a greater glucose-reduction effect compared to glargine (a type of insulin). [9]
10. In patients with type 2 diabetes and inadequate glycemic control, the administration of tirzepatide in addition to glargine resulted in significant improvements in glycemic control after 40 weeks. [10]
11. In T2D patients, tirzepatide was superior to semaglutide when it comes to the mean change in blood sugar levels. [11]
12. A study showed that tirzepatide is a good candidate for the development of pharmacotherapies in treating obesity, diabetes, and neurodegenerative disorders. [12]
13. In T2D patients, tirzepatide showed significantly better efficacy with regard to glucose control and weight loss compared to dulaglutide, an anti-diabetic medication. [13]
14. In T2D patients, tirzepatide treatment resulted in significant improvement in glycemic control and body weight. [14]
15. In adults with T2D and inadequate glycemic control despite treatment with insulin glargine, additional treatment with tirzepatide resulted in significant improvements in glycemic control. [15]
16. In T2D patients, treatment with tirzepatide greatly improved insulin sensitivity (the body’s response to the effects of insulin). [16]
17. In Japanese patients with T2D, tirzepatide administration was well-tolerated and resulted in decreased blood sugar and body weight. [17]
18. A 72-week trial in obese participants found that 5 mg, 10 mg, or 15 mg of tirzepatide once weekly resulted in substantial and sustained reductions in body weight. [18]
19. Studies suggest that tirzepatide administration in patients with type 2 diabetes can improve insulin sensitivity and insulin secretory responses to a greater extent compared with other antidiabetic medications. [19-26]

B. Promotes Weight Loss

Tirzepatide promotes weight loss by affecting certain brain chemicals involved in food intake, energy expenditure, and fat deposition. It does this by acting on the glucagon-like peptide-1 (GLP-1) receptor, which reduces fat cells and enhances fat breakdown. Evidence suggests that these mechanisms are the key to weight loss:

1. In patients with T2D, tirzepatide treatment induced clinically significant weight loss. [1-4, 7-8, 13-15,18]
2. In T2D patients, tirzepatide administration resulted in greater weight reduction compared to semaglutide, an anti-diabetic medication. [27]
3. Weekly administration of tirzepatide and semaglutide resulted in significant weight reduction in patients with T2D. [28]
4. In T2D patients, tirzepatide administration resulted in a strong weight loss (greater than 5%). [29]
5. In obese/overweight adults, tirzepatide treatment resulted in successful weight loss. [30]

C. Lowers the Risk of Heart Disease

The beneficial effects of tirzepatide on body composition and blood sugar levels can all contribute to a healthy heart. Specifically, tirzepatide increases adiponectin, a protein hormone that regulates the breakdown of fatty acids. Increased adiponectin levels are associated with a lower risk of cardiovascular disease. [31] In addition, aside from blood sugar, tirzepatide can also protect against heart problems by lowering the levels of triglycerides (blood fat). [32]

Studies suggest that tirzepatide can lower the risk of cardiovascular disease:

1. In participants with T2D, tirzepatide was safe and did not increase the risk of major cardiovascular events. [33]
2. In patients with T2D, tirzepatide successfully decreased biomarkers associated with cardiovascular risks such as YKL-40 (also known as chitinase-3 like-protein-1), intercellular adhesion molecule 1 (ICAM-1), leptin, and growth differentiation factor 15. [34]
3. Tirzepatide can lower the risk of cardiovascular disease by acting on the GLP-1 receptor, which in turn reduces cardiovascular risk factors such as hypertension, high lipid levels, obesity, increased inflammation, and endothelial cell dysfunction (constriction of the blood vessels of the heart). [35]

D. Improves Liver Health

Tirzepatide also has the ability to improve liver health by reducing liver fat. This beneficial effect is backed by a number of studies:

1. In T2D patients, high doses of tirzepatide significantly decreased nonalcoholic steatohepatitis-related biomarkers while increasing adiponectin, a protein hormone involved in fatty acid breakdown. [36]
2. In adult patients with T2D, tirzepatide treatment resulted in reduced liver fat. [37]
3. In patients with liver abnormalities, tirzepatide significantly improved several liver biomarkers such as liver fat. [38]
4. In patients with metabolic-associated fatty liver disease (MAFLD), treatment with tirzepatide resulted in a significant reduction in nonalcoholic steatohepatitis-related biomarkers such as liver enzymes. [39]
5. In patients with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), tirzepatide treatment resulted in a better reduction in liver fat content compared to dulaglutide, an anti-diabetic medication. [40]

Associated Side Effects of Tirzepatide

Tirzepatide 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 tirzepatide. 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 tirzepatide. Despite this, it was listed as a side effect associated with tirzepatide even though these associated side effects are very uncommon.

Side effects associated with tirzepatide may include the following:

• Constipation
• Diarrhea
• Nausea
• Vomiting

Is Tirzepatide better than Semaglutide?

As a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), tirzepatide produces synergistic effects like increased insulin production and release, which gives it an edge over strict GLP-1 receptor agonist such as semaglutide.

An overwhelming body of clinical evidence suggests that tirzepatide is superior to the anti-diabetic medication semaglutide with regards to improving blood sugar levels and reducing body weight:

1. In T2D patients, tirzepatide was superior to semaglutide when it comes to the mean change in blood sugar levels. [11]
2. In T2D patients, tirzepatide treatment for 28 weeks resulted in significant improvements in total insulin secretion rate and insulin sensitivity compared with semaglutide. [16]
3. In T2D patients, tirzepatide administration resulted in greater weight reduction compared with semaglutide. [20]
4. Weekly administration of tirzepatide in diabetic patients resulted in significant weight reduction than semaglutide. [33]
5. The SURPASS-2 study involving patients with type 2 diabetes found that tirzepatide is superior to semaglutide in improving HbA1c levels, body weight, fasting blood sugar, and self-monitored blood sugar levels. [41]
6. Available data from 2 short-term randomized trials suggest that tirzepatide is more effective than semaglutide in reducing HbA1c levels and body weight in patients with type 2 diabetes and obesity. [42]
7. In participants with T2D who were taking metformin, once-weekly administration of tirzepatide significantly reduced HbA1c levels and body weight compared with semaglutide. [43]
8. In patients with T2D, the administration of tirzepatide 5/10/15 mg for 40 weeks produced greater reductions in HbA1c and weight compared with semaglutide 2 mg. [44]
9. In patients with T2D, tirzepatide was superior to semaglutide with regard to improvement in HbA1c levels and resulted in greater weight reductions with similar overall side effects. [45]
10. In patients with T2D who have abnormal blood sugar levels, tirzepatide 5 mg, 10 mg, and 15 mg demonstrated superiority versus semaglutide 1 mg and titrated insulin degludec (iDeg) in improving HbA1c levels at 40 weeks and 52 weeks. [46]
11. In patients with T2D who were on metformin, higher doses of tirzepatide (10 mg and 15 mg) resulted in greater improvements in health-related quality of life and weight-related quality of life outcomes compared with semaglutide. [47]
12. In people with T2D, treatment with tirzepatide 15 mg substantially improved blood sugar control and insulin sensitivity at week 28 compared with 1 mg semaglutide. [48]
13. In people with T2D, treatment with tirzepatide 5 mg and 15 mg significantly improved markers of islet cell function and insulin sensitivity compared with 1 mg semaglutide. [49]
14. The administration of tirzepatide in diabetic patients produced greater weight loss and improvements in blood sugar levels compared with semaglutide. [50]
15. In patients with T2D, tirzepatide significantly reduced HbA1c, a marker of blood sugar levels, compared with semaglutide. [51]

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