Tirzepatide Reduces HbA1c and Body Weight Significantly More than Placebo or Semaglutide Irrespective of Baseline Beta-Cell Function-Post Hoc Analysis from SURPASS-1 and SURPASS-2

Tirzepatide (TZP), a once-weekly GIP/GLP-1 receptor agonist, achieved significantly greater HbA1c and body weight (BW) reductions with all doses (5, 10, 15 mg) vs placebo (SURPASS-1 [S-1]) and semaglutide (SEMA) 1 mg (SURPASS-2 [S-2]) in randomized Phase 3 trials in people with type 2 diabetes controlled by diet and exercise (S-1) or metformin (S-2). Exploratory post hoc analyses examined changes from baseline in HbA1c and BW in these studies at 40 weeks across HOMA2-B (C-peptide) and HOMA2-IR (insulin) quartiles (Q) from low (lower beta-cell function/insulin resistance) (Q1) to high (Q4) as assessed by mixed model repeated measures (MMRM). HbA1c reductions were greater with all TZP doses than placebo or SEMA within each HOMA2-B and HOMA2-IR baseline Q. HbA1c reductions were largest in people within HOMA-2B Q1, yet similar across all HOMA2-IR Qs (Fig). BW reductions were greater across Qs with all TZP doses (ranging from 6%-14%) than placebo (up to 2%) or SEMA (up to 7%). TZP was more efficacious than placebo or SEMA in reducing HbA1c and BW across a spectrum of pancreatic beta-cell function, notably achieving greater glycemic improvement in people with markers of diminished pancreatic beta cell function at baseline. Disclosure J.M.Maldonado: Employee; Eli Lilly and Company. C.De block: Advisory Panel; Abbott Diagnostics, Indigo Diabetes, Insulet Corporation, Eli Lilly and Company, Novo Nordisk, Research Support; Boehringer-Ingelheim, AstraZeneca, Indigo Diabetes, Eli Lilly and Company, Speaker's Bureau; Novo Nordisk. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Brown: Employee; Eli Lilly and Company. H.Wang: None. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company