957-P: Efficacy of Oral Semaglutide According to Background Medication: An Exploratory Subgroup Analysis of the PIONEER Trial Program

The global PIONEER program investigated the efficacy and safety of the first oral glucagon-like peptide-1 receptor agonist, oral semaglutide. Across PIONEER trials, patients with type 2 diabetes (T2D) were randomized to once-daily oral semaglutide (3, 7, 14 mg or flexibly dosed) or comparator. The present exploratory subgroup analysis evaluated the effect of background medications on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of trial (week 26, 52 or 78) in five PIONEER trials (3-5, 7-8). Data were analyzed from patients who received oral semaglutide or comparator (sitagliptin, liraglutide or placebo) based on background medication received: metformin, sulfonylurea, sodium-glucose co-transporter 2 inhibitor, insulin or combinations. Baseline characteristics were generally similar across subgroups. Reductions in HbA1c and BW were greater for oral semaglutide vs. comparators (except liraglutide, with similar HbA1c reductions), regardless of background medication (Table). In general, there were no statistically significant interactions between treatment and subgroups. Estimated treatment differences were consistent within each trial and background medication subgroups. These findings support the use of oral semaglutide across a broad population of patients with T2D in combination with other commonly used glucose-lowering agents. Disclosure J.B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Neurimmune. Research Support; Self; American Diabetes Association, National Institutes of Health, Novo Nordisk A/S, Patient-Centered Outcomes Research Institute, Sanofi, Tolerion, Inc., vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings, Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg Therapeutics, Novo Nordisk A/S, Senseonics, Inc, vTv Therapeutics, Zafgen, Inc. M. Crowley: None. J.W. Eriksson: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. M. Gislum: Employee; Self; Novo Nordisk A/S. C.L. Hertz: Employee; Self; Novo Nordisk A/S. M. Kaiser: Advisory Panel; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes. A. Moeller Nielsen: Employee; Self; Novo Nordisk A/S. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S. Funding Novo Nordisk A/S