Tirzepatide

A. Lowers Blood Sugar Levels

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. GLP-1 and GIP are hormones involved in the control of blood sugar levels. 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.

Tirzepatide works by stimulating the release of insulin in a glucose-dependent manner, meaning that it is more effective at lowering blood sugar levels when blood sugar levels are high. In other words, tirzepatide is more effective at helping people with type 2 diabetes control their blood sugar levels when they have eaten a meal or snack that has caused their blood sugar levels to rise. This is because tirzepatide is designed to mimic the action of two gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are released in response to food intake and help to regulate blood sugar levels.

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 able to safely and effectively improve blood sugar levels and body weight. [5]
6. In T2D patients, once weekly subcutaneous injection of tirzepatide resulted in a significant reduction in overall blood sugar levels with a lower risk of adverse events compared to placebo treatment. [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 an 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 control of blood sugar levels, the administration of tirzepatide in addition to other diabetes medicines, such as insulin glargine, resulted in improved blood sugar 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 the control of blood sugar levels and body weight. [14]
15. In adults with T2D and inadequate control of blood sugar levels despite treatment with insulin glargine, additional treatment with tirzepatide resulted in significant improvements in the control of blood sugar levels. [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 as well as lower adverse events. [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 body weight reductions. [18]
19. In five clinical trials involving individuals with type 2 diabetes (SURPASS 1-5), tirzepatide administered at 5 mg, 10 mg, or 15 mg per week demonstrated unprecedented reductions in HbA1c (1.24 to 2.58%) and body weight (5.4-11.7 kg). A notable percentage of patients (23.0 to 62.4%) achieved an HbA1c below 5.7%, indicating normoglycemia (normal blood sugar levels), and a substantial portion (20.7 to 68.4%) experienced more than 10% baseline body weight loss. Notably, tirzepatide exhibited superior efficacy in decreasing HbA1c and body weight compared to selective GLP-1 RA semaglutide (1.0 mg per week) and titrated basal insulin. It was also observed that patients receiving insulin without tirzepatide tended to gain weight during the study. [19]
20. 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. [20-26]

B. Helps Lose Weight

<img decoding="async" class="size-full wp-image-20074 alignnone entered exited" title="" src="data:;base64,” alt=”Close-up of person’s feet on a scale, suggesting weight loss.” width=”945″ height=”630″ data-lazy-srcset=”https://www.genemedics.com/wp-content/uploads/2022/06/Tirzepatide-Helps-Lose-Weight.png 945w, https://www.genemedics.com/wp-content/uploads/2022/06/Tirzepatide-Helps-Lose-Weight-300×200.png 300w, https://www.genemedics.com/wp-content/uploads/2022/06/Tirzepatide-Helps-Lose-Weight-768×512.png 768w” data-lazy-sizes=”(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 1362px) 62vw, 840px” data-lazy-src=”https://www.genemedics.com/wp-content/uploads/2022/06/Tirzepatide-Helps-Lose-Weight.png” />

Mounjaro tirzepatide is approved as a weight loss medication for overweight adults with at least one associated health problem. The FDA approved tirzepatide on June 7, 2022, for this indication.

In clinical trials, tirzepatide was shown to be effective in helping overweight adults with at least one associated health problem lose weight. In one trial, tirzepatide was shown to cause weight loss of up to 22% in people with a BMI of 30 or higher and at least one associated health problem.

Like other weight loss drugs, 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. The SURMOUNT-2 trial for tirzepatide (phase 3 trial) found that participants taking tirzepatide 5 mg, 10 mg, or 15 mg once weekly for 72 weeks achieved average weight reductions of 16.4%, 20.9%, and 22.5% for the 5 mg, 10 mg, and 15 mg tirzepatide groups compared to 2.4% for the placebo group. The rates of treatment discontinuation because of adverse events stood at 3.8% (10 mg), 7.4% (15 mg), and 3.8% (placebo). [27]
2. In patients with T2D, tirzepatide treatment induced clinically significant weight loss. [1-4, 7-8, 13-15,18]
3. In T2D patients, tirzepatide administration resulted in greater body weight reductions compared to semaglutide, an anti-diabetic medication. Gastrointestinal symptoms (nausea, vomiting, and diarrhea) were the most frequently reported adverse events, and they were mostly of mild to moderate intensity in both the tirzepatide and semaglutide groups. [28]
4. Weekly administration of tirzepatide and semaglutide resulted in significant weight reduction in patients with T2D. [29]
5. In T2D patients, tirzepatide treatment regimen resulted in a strong weight loss (greater than 5%). [30]
6. In obese/overweight adults, tirzepatide treatment resulted in successful weight loss. [31]

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. [32] In addition, aside from blood sugar, tirzepatide can also protect against heart problems by lowering the levels of triglycerides (blood fat). [33]

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

1. In participants with T2D, tirzepatide treatment regimen (5 mg, 10 mg, and 15 mg) was safe and did not increase the risk of major cardiovascular events. [34]
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. [35]
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). [36]

D. Improves Liver Health

<img decoding="async" class="size-full wp-image-20071 alignnone entered exited" title="" src="data:;base64,” alt=”tirzepatide improves liver health” width=”945″ height=”630″ data-lazy-srcset=”https://www.genemedics.com/wp-content/uploads/2022/06/Improves-Liver-Health.png 945w, https://www.genemedics.com/wp-content/uploads/2022/06/Improves-Liver-Health-300×200.png 300w, https://www.genemedics.com/wp-content/uploads/2022/06/Improves-Liver-Health-768×512.png 768w” data-lazy-sizes=”(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 1362px) 62vw, 840px” data-lazy-src=”https://www.genemedics.com/wp-content/uploads/2022/06/Improves-Liver-Health.png” />

GIP and GLP-1 are natural incretin hormones that play a role in liver function. They can help to protect the liver from damage, promote the regeneration of liver cells, and improve liver function. Here are some specific ways that GIP and GLP-1 contribute to improving liver health:

• Protect the liver from damage: GIP and GLP-1 can help to protect the liver from damage caused by toxins, such as alcohol and fat. They do this by increasing the production of antioxidants and by reducing the production of free radicals. Free radicals are unstable molecules that can damage cells, including liver cells.
• Promote the regeneration of liver cells: GIP and GLP-1 can help to promote the regeneration of liver cells after injury. They do this by stimulating the production of growth factors, which are proteins that help cells to grow and repair themselves.
• Improve liver function: GIP and GLP-1 can improve liver function by increasing the production of bile and by reducing the production of liver enzymes. Bile is a fluid that helps to digest fats and remove toxins from the body. Liver enzymes are proteins that help the liver metabolize drugs and toxins.

Tirzepatide also has the ability to improve liver health by reducing liver fat. A number of studies backs this beneficial effect:

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. [37]
2. In adult patients with T2D, tirzepatide treatment resulted in reduced liver fat. [38]
3. In patients with liver abnormalities, tirzepatide significantly improved several liver biomarkers such as liver fat. [39]
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. [40]
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. [41]

E. Improves Kidney Function

Tirzepatide has shown a potential to improve kidney function through its multifaceted mechanism of action. By promoting glucose control, reducing insulin resistance, and mitigating inflammation, tirzepatide can help alleviate the metabolic stress on the kidneys. Additionally, its GLP-1 receptor agonist component has been associated with vasodilation and decreased glomerular hyperfiltration, which could contribute to preserving kidney function.

Studies support the beneficial effects of tirzepatide on overall kidney function:

1. In the SURPASS-4 trial, the dual GIP and GLP-1 receptor agonist tirzepatide exhibited superior effects over titrated daily insulin glargine in people with type 2 diabetes and high cardiovascular risk. This trial showcased that tirzepatide not only reduced HbA1c concentrations, body weight, and blood pressure more effectively, but it also demonstrated a notable impact on kidney parameters.A post-hoc analysis of the trial revealed that tirzepatide led to a slower rate of estimated glomerular filtration rate (eGFR) decline and significantly reduced urine albumin-creatinine ratio (UACR) when compared to insulin glargine. This effect was also observed in participants who did not fulfill the CKD criteria outlined by either eGFR or albuminuria according to KDIGO guidelines. These findings highlight the potential of tirzepatide to positively influence kidney function in individuals with type 2 diabetes and heightened cardiovascular risk. [42]
2. A study reported that tirzepatide could pave the way for a new type of diabetes and weight management medication. [43] Beyond its action on certain receptors, there’s ongoing research on even more powerful versions that could help control weight and boost energy usage. These potential effects on kidney health could help prevent and treat CKD.