227-OR: Tirzepatide Reduces HbA1c and Body Weight Significantly More than Placebo Regardless of Insulin Sensitivity and Beta-Cell Function—Post Hoc Analysis from SURMOUNT-2

Treatment with tirzepatide (TZP) led to substantial improvements in body weight (BW) and glycemia compared to placebo in participants with obesity and type 2 diabetes (T2D) in SURMOUNT (SM)-2. In this analysis, we assessed whether baseline markers of pancreatic beta cell function and insulin sensitivity were associated with the magnitudes of BW and glycemic reductions. Post hoc analyses examined changes from baseline in BW and HbA1c in SM-2 at 72 weeks across HOMA2-B (computed with C-peptide) and HOMA2-IR (computed with insulin) quartiles (Q) from low (lower beta cell function/insulin resistance) (Q1) to high (Q4) as assessed by a mixed model for repeated measures using efficacy estimand. BW and HbA1c reductions were greater with TZP 10 mg and 15 mg than placebo within each HOMA2-B and HOMA2-IR baseline Q. More participants across all Qs achieved ≥15% BW reduction with TZP (36-63%) than placebo (up to 4%). More participants across all Qs reached HbA1c 5.7% with TZP (ranging from 42-71%) than placebo (up to 6%). TZP was more effective than placebo in reducing BW and HbA1c regardless of beta cell function and insulin resistance in participants with obesity and T2D. BW reductions with TZP trended greater with higher beta cell function, whereas HbA1c reduction trended greater with lower beta cell function. Disclosure T. Heise: Research Support; ADOCIA, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk A/S. Consultant; Gan Eli Lilly and Company. Research Support; Altimmune Inc., Sanofi, Zealand Pharma A/S, BIOTON, Civica Foundation, Enyo Pharma, Gan Eli Lilly and Company. I. Benabbad: Employee; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Liao: Employee; Eli Lilly and Company.