798-P: Semaglutide Effect during Mixed-Meal Tolerance Test (MMTT) with Fully Closed-Loop Therapy in Type 1 Diabetes (T1D)

Introduction and Objective: We assessed glycemia, insulin needs, and C-peptide levels with semaglutide after MMTT in type 1 diabetes. Methods: This is a sub-analysis of a randomized crossover trial assessing semaglutide vs. placebo with automated insulin delivery (AID) in adults with T1D (NCT05205928). Participants performed a MMTT with 6 mL/kg of Boost, while using fully-closed-loop AID, after 12 weeks of semaglutide and placebo, in random order. Plasma glucose and C-peptide levels were measured over 120 minutes. C-peptide levels <0.003 nmol/L assumed to be 0 nmol/L. Paired t-test was performed for parametric comparisons, with Wilcoxin signed-rank test for non-parametric comparisons. Results: Ten participants completed the MMTT, with 8 having C-peptide levels and 7 having pump data; 40% were female, with age 47 (SD 14) years and T1D duration 29 (11) years. All but one had baseline C-peptide of < 0.003 pmol/L. Semaglutide reduced glucose AUC compared to placebo (p=0.006), but C-peptide AUC was not different between arms (p=0.35). Despite having lower glucose AUC, the insulin delivery by the AID was lower for semaglutide than placebo (p = 0.024). Conclusion: Semaglutide reduced glucose AUC during fully closed-loop therapy after weight-adjusted meal replacement, with less insulin output required from the AID. Further studies are needed to understand mechanistic of effects. Disclosure M. Pasqua: Speaker's Bureau; Abbott, Sanofi, Medtronic. J. Doumat: None. A. Jafar: None. M. Tsoukas: Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc, Sanofi. A. Haidar: Research Support; Tandem Diabetes Care, Inc. Consultant; Eli Lilly and Company, Abbott. Research Support; ADOCIA, Dexcom, Inc., Ypsomed AG, Bigfoot Biomedical, Inc. Funding Canada Research Chair in Artificial Pancreas Systems.