1665-P: Analysis of Glucose Biomarkers in Phase I and Phase II Studies of Survodutide in People with Type 2 Diabetes or Living with Overweight/Obesity

Introduction & Objective: Survodutide, a glucagon receptor/glucagon-like peptide-1 receptor (GCGR/GLP-1R) dual agonist, elicited greater HbA1c reduction up to -1.71% vs semaglutide 1 mg (-1.47%) in a Phase 2 trial in patients with type 2 diabetes. This analysis evaluated changes in insulin sensitivity, pancreatic islet cell function, and glucose biomarkers from three Phase I/II trials of survodutide. Methods: Descriptive statistics were derived from a Phase 2 trial in patients living with obesity/overweight without diabetes (NCT04667377), a Phase 2 trial in patients with type 2 diabetes (NCT04153929), and a Phase 1 study in patients living with obesity/overweight (NCT03591718). Results: High survodutide doses improved insulin sensitivity as reflected in a decrease in mean absolute HOMA-IR scores from baseline (BL) to the end of treatment (EOT), in contrast to no change or increase with placebo (PBO): NCT04667377, -1.1 (4.8 mg QW) vs -0.2 at Week 46; NCT04153929, -0.9 (1.8 mg twice weekly [BIW]) vs 0.9 at Week 17; and NCT03591718, -1.0 (2.4 mg BIW following up titration) vs 0.3 at Week 16. Survodutide improved HOMA-β, with mean percentage change from BL to EOT consistently higher vs PBO: NCT04667377, 8.6% vs -1.1%; NCT04153929, 88.0% vs 18.0%. In NCT04667377, change from BL to Week 46 in FPG with survodutide vs PBO was 0.4 vs 0.0 mmol/L. Change from BL in insulin and non-fasting plasma glucose levels with survodutide 4.8 mg vs PBO, was -23.4 vs 0.4 pmol/L and -0.0 vs 0.6 mmol/L, respectively. Additionally, mean change from BL to Week 46 in adiponectin, glucagon, and c-peptide levels with survodutide 4.8 mg vs PBO was 1.9 vs -0.15 mg/L, -15.2 vs -0.8 pmol/L, and -0.1 vs 0.0 nmol/L, respectively. Conclusion: Survodutide treatment showed improvement in markers of insulin sensitivity, pancreatic islet cell function, and glucose biomarkers, in patients living with obesity/overweight and those with type 2 diabetes. Disclosure E.I. Ekinci: Advisory Panel; Lilly Diabetes. Research Support; Novo Nordisk, Boehringer-Ingelheim, Eli Lilly and Company. Board Member; Eli Lilly and Company. Advisory Panel; Abbott. Research Support; Endogenex, Versanis, AstraZeneca. J. Martinez: Employee; Boehringer-Ingelheim. A.M. Hennige: Employee; Boehringer-Ingelheim. C. Schölch: Employee; Boehringer-Ingelheim. Funding Boehringer Ingelheim