964-P: Glycemic and Body Weight Responses to Oral Semaglutide in the PIONEER Trial Program

Abstract

The PIONEER phase 3 program investigated glycemic response and other efficacy endpoints in patients (pts) with type 2 diabetes randomized to the glucagon-like peptide-1 analog oral semaglutide (sema; 3, 7 or 14 mg once daily), placebo (pbo) or an active comparator (empagliflozin [empa] 25 mg, sitagliptin [sita] 100 mg or liraglutide [lira] 1.8 mg once daily). This post-hoc analysis of the PIONEER 1-5 and 8 trials evaluated the response of any reduction in HbA1c (%) and/or body weight (%), and a clinically relevant composite endpoint of HbA1c reduction ≥1% and body weight loss ≥5%, with oral sema 14 mg vs. comparators at the end of treatment (26-78 weeks). Across trials, any reduction in HbA1c was observed in higher proportions of pts with oral sema (89-95%) than with pbo (51-64%) or active comparators (82-88%). A simultaneous reduction in both HbA1c and body weight was seen in 72-86% of pts treated with oral sema (Figure). The composite of HbA1c reduction ≥1% and body weight loss ≥5% was achieved by 27-41% of pts with oral sema, 1-8% of pts with pbo, 11% with sita 100 mg, 18% with lira 1.8 mg, and 20% with empa 25 mg. Within each trial, the odds of achieving HbA1c reduction of ≥1% and body weight loss of ≥5% with oral sema 14 mg were significantly greater vs. all comparators (p<0.0001). These results demonstrate that oral sema 14 mg was more effective vs. comparators for providing any HbA1c reduction, or both an HbA1c reduction ≥1% and body weight loss ≥5%. Disclosure K.M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Elsevier. Research Support; Self; Novo Nordisk Inc., Sanofi-Aventis. Speaker’s Bureau; Self; Nova Biomedical. Other Relationship; Self; UpToDate, Vizient Inc. C.L. Hertz: Employee; Self; Novo Nordisk A/S. L. Mellbin: Advisory Panel; Self; Amgen, AstraZeneca, Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; AstraZeneca, Bayer AG, Novo Nordisk A/S. Research Support; Self; Bayer AG. Speaker’s Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk Foundation. M. Abildlund Nielsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. R. Sørrig: Employee; Self; Novo Nordisk A/S. V.C. Woo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. Funding Novo Nordisk A/S