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.
Keywords: beta-cell function; incretin; insulin sensitivity; tirzepatide; type 2 diabetes.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.