Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2)

Abstract Context In previous SURPASS studies tirzepatide reduced HbA1c and body weight and improved markers of insulin sensitivity (IS) and beta-cell function to a greater extent than comparators. Objective Explore changes in biomarkers of beta-cell function and IS and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide. Design Post-hoc analysis of SURPASS-2 Phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks). Setting Post-hoc analysis of 128 sites in 8 countries. Participants 1879 participants with T2D. Interventions Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg. Main outcomes measures Change in HOMA2-B, HOMA2-IR, fasting glucagon, fasting C-peptide, and fasting insulin. Results At week 40, greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9 to 120.4%) than with semaglutide 1 mg (84.0%) [p<0.05]. There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5 to 24.0%) than with semaglutide 1 mg (5.1%) [p<0.05]. Tirzepatide 10 and 15 mg resulted a significant reduction in both fasting C-peptide (5.2 to 6.0%) and fasting glucagon (53.0 to 55.3%) compared to an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg [p<0.05]. HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile. Conclusion In this post-hoc analysis improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, irrespective of baseline beta cell function and insulin resistance, compared to semaglutide