Tirzepatide: A Comprehensive Clinical and Pharmacological Monograph

Executive Summary

Tirzepatide represents a paradigm shift in the management of type 2 diabetes mellitus (T2DM) and chronic weight management, establishing a new therapeutic class as the first-in-class, unimolecular dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors.[1] Developed by Eli Lilly and Company, this synthetic 39-amino acid peptide, marketed as Mounjaro® for T2DM and Zepbound® for chronic weight management and obstructive sleep apnea (OSA), has demonstrated unprecedented efficacy in both glycemic control and weight reduction across a comprehensive suite of clinical trials.[3] Its unique "twincretin" mechanism of action leverages the synergistic effects of two key incretin hormones to provide metabolic benefits that surpass those of selective GLP-1 receptor agonists (RAs), the previous therapeutic benchmark.[5]

The landmark SURPASS clinical trial program, which evaluated Tirzepatide in diverse populations with T2DM, consistently showed superior, dose-dependent reductions in hemoglobin A1c (HbA1c) and body weight when compared against placebo, the selective GLP-1 RA semaglutide, and various basal insulins.[7] A significant proportion of patients treated with higher doses of Tirzepatide achieved normoglycemia (HbA1c <5.7%), a level of glycemic control that challenges traditional treatment goals and suggests a potential for disease modification.[8]