Tirzepatide 20mg

▎Tirzepatid Structure

Source: PubChem

Sequence: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diacid-C20-gamma-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Molecular Formula: C225H348N48O68 Molecular Weight: 4813 g/mol CAS Number: 2023788-19-2 PubChem CID: 163285897 Synonyms: Zepbound; Mounjaro

▎Tirzepatid Research

What is the research background of Tirzepatid?

The research background of Tirzepatid primarily stems from the exploration of diabetes treatment drugs and the demand for weight management drugs. Traditional diabetes treatment drugs have limitations, while GLP-1 receptor agonists demonstrate significant efficacy in improving blood glucose control, prompting researchers to develop more effective drugs of the same class. As a GIP/GLP-1 dual receptor agonist, Tirzepatid can better regulate blood glucose levels. The global increase in overweight and obese populations has made weight control an urgent clinical need. GLP-1 receptor agonists have weight-reducing effects, making them a target for weight loss. Tirzepatid has gained attention due to its favorable weight-loss outcomes.

What is the mechanism of action of Tirzepatid?

Dual receptor agonist action: 

Tirzepatid is a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist [1,2](Wong E, 2023; Kumar D, 2022). GLP-1 and GIP are both incretin hormones produced in the intestine, playing a crucial role in maintaining glucose homeostasis. Tirzepatid exerts a synergistic effect by simultaneously activating GLP-1 and GIP receptors, thereby regulating blood glucose levels.

Regulation of insulin and glucagon secretion: 

It increases insulin synthesis and secretion while reducing glucagon release in a glucose-dependent manner. When blood glucose levels rise, Tirzepatid stimulates pancreatic β-cells to secrete insulin, promoting glucose uptake and utilization, thereby lowering blood glucose levels; simultaneously, it inhibits pancreatic α-cells from secreting glucagon, reducing hepatic glucose output, further lowering blood glucose levels, and effectively controlling fasting and postprandial blood glucose levels^[1,3].

Other mechanisms of action: 

Tirzepatid also promotes satiety, which may be related to activating GLP-1 receptors, acting on the central nervous system, and influencing appetite regulation centers, leading patients to reduce food intake and thereby aiding in weight loss. It also delays gastric emptying, prolonging the time food remains in the stomach and slowly entering the small intestine, thereby preventing rapid increases in blood glucose levels^[1].

Figure 1 Mechanism of action of Tirzepatide ^[6].

What are the applications of Tirzepatide?

Treatment of type 2 diabetes: 

Tirzepatid is approved for the treatment of adult patients with type 2 diabetes as an adjunct to diet and exercise. The SURPASS trial demonstrated that Tirzepatid significantly reduces hemoglobin A1c (HbA1c) levels, with reductions ranging from -1.87% to -2.59% (-20 to -28 mmol/mol). It also demonstrates superior glycemic control compared to certain GLP-1 receptor agonists, such as semaglutide 1 mg in the SUPRASS-2 trial. Additionally, it can reduce body weight, with weight loss ranging from -6.2 to -12.9 kg in clinical studies, which is particularly significant for patients with type 2 diabetes who often have overweight or obesity issues ^[1,4].

Obesity treatment: 

Since Tirzepatid promotes satiety, reduces food intake, and promotes weight loss, it has potential therapeutic value for patients with obesity. Studies show that it can reduce weight by over 20%, improve patients’ metabolic status, and serve as a new treatment option for obesity, helping obese patients lose weight and reduce the risk of various diseases associated with obesity^[1,2].

Reduced risk of cardiovascular disease: 

Patients with type 2 diabetes often face an increased risk of cardiovascular disease. In addition to lowering blood sugar and weight, Tirzepatid has positive effects on cardiovascular-related indicators, including reducing blood pressure, decreasing visceral fat accumulation, and lowering circulating triglyceride levels, thereby helping to reduce the risk of cardiovascular disease and improve patients’ cardiovascular outcomes^[4].

Potential treatment for non-alcoholic steatohepatitis (NASH): 

Tirzepatid has potential therapeutic effects on NASH. By improving insulin sensitivity and regulating glucose and lipid metabolism, it can reduce hepatic steatosis and inflammation, offering a new direction for NASH treatment^[5].

Conclusion

As a GIP/GLP-1 dual receptor agonist, Tirzepatid has demonstrated significant efficacy in the treatment of diabetes and metabolic disorders. By regulating insulin and glucagon secretion, delaying gastric emptying, and enhancing satiety, it effectively lowers hemoglobin A1c levels and reduces patient weight. Additionally, the drug improves cardiovascular risk factors such as lipid levels and blood pressure and demonstrates efficacy in non-alcoholic steatohepatitis.