Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1 receptor agonists. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight. Tirzepatide is in phase 3 development for blood glucose management in adults with type 2 diabetes and for chronic weight management. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH).
Glucagon-like peptide-1 (GLP-1) lowers blood glucose by several mechanisms, including stimulating insulin secretion and suppressing glucagon secretion during hyperglycemia. Glucose-dependent insulinotropic polypeptide (GIP) also stimulates insulin release during hyperglycemia, but it also stimulates glucagon release during hypoglycemia. Thus, a dual agonist for both GLP-1 and GIP receptors theoretically could enhance glycemic control while minimizing hypoglycemia in patients with type 2 diabetes. Tirzepatide is a dual agonist for both receptors. Researchers have examined its effects in two industry-sponsored randomized trials that involved patients with type 2 diabetes.
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