727-P: Glycemic Effect of Tirzepatide by Duration of Diabetes

Results of SURPASS-1 through -5 trials have shown robust efficacy of novel dual GIP/GLP-1 receptor agonist tirzepatide (TZP) in people with type 2 diabetes. To understand whether glucose-lowering effect of tirzepatide depends on the duration of diabetes we conducted a subgroup analysis within each of the 5 Phase 3 trials. The primary endpoint of the 5 SURPASS clinical trials was mean change from baseline in HbA1c for 5mg, 10mg, and 15mg to 40 or 52 weeks against various comparators in adults with type 2 diabetes. This subgroup analysis of the 5 trials assessed whether mean change of HbA1c from baseline in the overall population were consistent when assessed by baseline duration of diabetes category (≤5 years, 5 to years, >years) in patients while they were on-treatment and without rescue medication (efficacy estimand) . For all 5 studies, analysis of change from baseline in HbA1c at 40 or 52 weeks for all 3 duration of diabetes subgroups were consistent with primary study results, with the treatment differences favoring all 3 doses of TZP compared with placebo or active comparator (Figure) . The most frequent adverse events were mild-to-moderate, gastrointestinal-related and occurred during the dose-escalation period. In conclusion, these results suggest that TZP was effective for mean change from baseline Hba1c for patients regardless of baseline duration of diabetes consistent with the overall patient population across the 5 SURPASS studies. Disclosure C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. C.Mathieu: Advisory Panel; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Imcyse, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca. H.Sapin: Employee; Eli Lilly and Company. J.I.Kiljanski: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Peleshok: Employee; Eli Lilly and Company, Eli Lilly and Company.