At week 40, tirzepatide doses resulted in a 96.9-120.4% increase in pancreatic β-cell function compared to an 84.0% increase with semaglutide.
Tirzepatide significantly improved β-cell function, as indicated by changes, more than semaglutide.
All doses of tirzepatide resulted in a greater reduction in insulin resistance () compared to semaglutide.
Tirzepatide 10 and 15 mg led to significant reductions in both fasting C-peptide and fasting glucagon, while semaglutide showed an increase in C-peptide.
Reductions in HbA1c and body weight were consistently greater with tirzepatide across all levels of baseline β-cell function and insulin resistance.
Simplified
CONTEXT: In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and β-cell function to a greater extent than comparators.
OBJECTIVE: Explore changes in biomarkers of β-cell function and insulin sensitivity 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: A total of 1879 participants with type 2 diabetes.
MAIN OUTCOMES MEASURES: Change in homeostatic model assessment indices for pancreatic β-cell function () and for insulin resistance (), fasting glucagon, fasting C-peptide, and fasting insulin.
RESULTS: At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P < .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P < .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, regardless of baseline β-cell function and insulin resistance, compared with semaglutide.
Key numbers
96.9% to 120.4%
Increase in
Percent change from baseline at week 40 with tirzepatide vs semaglutide.
15.5% to 24.0%
Reduction in
Percent change from baseline at week 40 with tirzepatide vs semaglutide.
−2.09% to −2.46%
HbA1c Reduction
Change from baseline to week 40 for tirzepatide vs semaglutide.
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