2835-LB: Greater Combined A1C Reductions and Weight Loss with 25 mg and 50 mg vs. 14 mg Oral Semaglutide in Adults with T2D: Evidence from PIONEER PLUS

Introduction and Objective: PIONEER PLUS investigated the efficacy and safety of oral semaglutide 25 mg and 50 mg vs 14 mg in adults with inadequately controlled T2D. Here, we compared 25 mg and 50 mg doses vs 14 mg dose regarding achievement of clinically meaningful composite endpoints for A1C and weight loss. Methods: PIONEER PLUS was a 68-week, multicenter, randomized, double-blind, phase 3b trial. Adults (≥ 18 years) with T2D (A1C 8.0%−10.5%) and BMI of ≥25.0 kg/m2 on 1-3 oral glucose-lowering medications were randomized 1:1:1 to once-daily oral semaglutide 14 mg, 25 mg, or 50 mg. In this post hoc analysis, the proportion of participants and odds of achieving composite A1C (7.0% and ≤6.5%) and weight loss (≥5% and ≥10%) target endpoints at weeks 26 and 52 were assessed. Results: Irrespective of the composite endpoint assessed, a higher percentage of participants met the endpoint with 25 mg and 50 mg vs 14 mg oral semaglutide. The estimated odds ratios were statistically significant in favor of 25 mg and 50 mg oral semaglutide vs 14 mg oral semaglutide for all composites and timepoints tested (all p0.0001; figure). Conclusion: The odds of achieving even the most stringent composite of ≤6.5% A1C and ≥10% weight loss were significantly higher with 25 mg and 50 mg vs 14 mg oral semaglutide already after 26 weeks. These findings support 25 mg and 50 mg oral semaglutide as a highly effective option to improve both glycemic control and weight loss in T2D. Disclosure J. Aberle: Speaker's Bureau; Current; AstraZeneca, Eli Lilly and Company. Advisory Panel; Current; Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Novo Nordisk, Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. P. Bogdanski: None. E. Ising: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. C.K. R: None. A. Jahagirdar: Employee; Current; Novo Nordisk. S.D. Pedersen: Advisory Panel; Current; Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Advisory Panel; Current; Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Bausch + Lomb, GlaxoSmithKline plc., Bayer AG. Advisory Panel; Current; Roche Canada. Research Support; Current; Roche Canada, Amgen Canada. Advisory Panel; Current; Amgen Canada. Research Support; Current; Regeneron Pharmaceuticals Inc. Advisory Panel; Current; AbbVie Inc. Research Support; Current; Pfizer Inc., AstraZeneca. Advisory Panel; Current; AstraZeneca.