337-OR: Tirzepatide Improved Markers of Islet-Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared with Semaglutide in People with Type 2 Diabetes

Tirzepatide (TZP) achieved significantly greater HbA1c and weight reductions with all doses (5, and 15 mg) vs. semaglutide 1 mg (SEMA) in a Phase 3 trial of 1879 people with type 2 diabetes (T2D) on background metformin (mean age 56.6 years; T2D duration 8.6 years; baseline HbA1c 8.3% [67 mmol/mol]; BMI 34.2 kg/m2) (SURPASS-2) . Changes in fasting markers of islet cell function and insulin sensitivity were assessed by mixed model repeated measures in the modified intent-to-treat population. At 40 weeks, all TZP doses improved HOMA2-B, calculated with C-peptide, as indicated by a significant increase by 97-120% on average with TZP, compared to 84% with SEMA. Fasting glucagon levels, adjusted for fasting serum glucose, significantly decreased by 53-55% on average with TZP and 15 mg doses compared with SEMA (48%) . All TZP doses improved insulin sensitivity as reflected by a significant decrease by 16-24% on average of HOMA2-IR, calculated with insulin, compared to a decrease by 5% with SEMA. Fasting insulin levels were also significantly reduced by 9-21% on average with all TZP doses compared to an increase of 0.6% with SEMA. Dual GIP/GLP-1 receptor agonist TZP significantly improved markers of islet cell function and insulin sensitivity compared to selective GLP-1 RA SEMA in people with T2D. Disclosure K. Brown: Employee; Eli Lilly and Company. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.K. Thomas: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Liu: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company