Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management

The combination of glucagon-like peptide-1 (GLP-1) with other gut hormones including the glucose-dependent insulinotropic peptide (GIP) has been explored to complement and enhance further the GLP-1 effects on glycemia and weight loss. Tirzepatide is the first dual co-agonist (acting on GLP-1/GIP receptors) which has been approved for treatment of type 2 diabetes mellitus (T2DM) based on the findings from the SURPASS programme (phase 3 clinical trials). The SURPASS 1-5 trials assessed the safety and efficacy of tirzepatide in people with T2DM of duration ranging from 4 to 14 years, from monotherapy through to insulin add-on in global populations, with another two trials dedicated to Japanese population. Over periods of treatment up to 104 weeks, once weekly tirzepatide 5, 10, and 15 mg reduced glycosylated hemoglobin (1.87% to 3.02%) and body weight (5.4 to 12.9 kg), improved multiple cardiometabolic risk factors (including reduction in liver fat, new-onset macroalbuminuria, blood pressure, and lipids) across the spectrum of T2DM. Tirzepatide 5 to 15 mg once weekly provided better efficacy than placebo and other commonly used glucose-lowering medications such as semaglutide 1 mg, dulaglutide, insulin degludec, and glargine. All tirzepatide doses were well tolerated with similar side-effect profile to the GLP-1 receptor analogues. The ongoing SURPASS-CVOT study will assess the cardiovascular safety of tirzepatide. In people without diabetes, tirzepatide 5 to 15 mg once weekly for the treatment for obesity (SURMOUNT-1) resulted in substantial reductions in body weight (16.5% to 22.4%) over 72 weeks. Overall, the SURPASS programme and SURMOUNT-1 study suggest that tirzepatide is marking a new era in T2DM and/or obesity management through dual agonism of gut hormones.