Application

Tirzepatide mechanism of action：effects on endocrine function and insulin resistance in patients with type 2 diabetes.Tirzepatide is a novel glucose-dependent insulinotropic polypeptide like peptide 1 (GLP-1) receptor agonist approved in the United States as an adjunct to diet and exercise to improve glycaemic control in adultswith type 2 diabetes and under investigation for use in chronic weight management, major adverse cardiovascular events and the management of other conditions, including heart failure with preserved ejectionfraction and obesity and non-cirrhotic non-alcoholic steatohepatitis. The Phase 3 SURPASS 1- 5 clinical trial programme was designed to assess efficacy and safety of once-weekly subcutaneously injected tirzepatide(5, 10 and 15 mg), as monotherapy or combination therapy, across a broad spectrum of people with type 2 diabetes. Use of tirzepatide in clinical studies was associated with marked reductions of glycatedhaemoglobin (-1.87 to -2.59%, -20 to -28 mmol/mol) and body weight (-6.2 to -12.9 kg), as well as reductions in parameters commonly associated with heightened cardiometabolic risk such as blood pressure,visceral adiposity and circulating triglycerides. In SUPRASS-2, these reductions were greater than with the GLP-1 receptor agonist sema 1 mg. Tirzepatide was well tolerated, with a low risk of hypoglycaemia whenused without insulin or insulin secretagogues and showed a generally similar safety profile to the GLP-1 receptor agonist class. Accordingly, evidence from these clinical trials suggests that tirzepatide offers a newopportunity for the effective lowering of glycated haemoglobin and body weight in adults with type 2 diabetes.