55-OR: Oral Semaglutide vs. Liraglutide and Placebo in T2D: PIONEER 4

Abstract

Patients (pts) with T2D uncontrolled on metformin ± SGLT2i were randomized to oral semaglutide (sema) 14 mg once daily (N=285), liraglutide (lira) 1.8 mg (N=284) or placebo (pbo, N=142) in a phase 3a, 52-week, double-blind, double-dummy trial (NCT02863419). Endpoints: Change (baseline to week 26) in HbA1c (primary) and body weight (BW, confirmatory secondary). Two estimands addressed two efficacy-related questions: Treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized pts. Treatment policy estimand: Oral sema was non-inferior (margin 0.4%) to lira and superior to pbo in reducing HbA1c, and superior to both in reducing BW at week 26 (Table). Differences in both HbA1c and BW were significant at week 52. Trial product estimand: Oral sema gave significant reductions in HbA1c and BW vs. lira and pbo at weeks 26 and 52. Oral sema had comparable tolerability to lira; 11% (oral sema) vs. 9% (lira) and 4% (pbo) prematurely discontinued trial product due to adverse events (primarily gastrointestinal; 5% [oral sema] vs. 3% [lira] discontinued due to nausea). In conclusion, oral sema was well tolerated in pts with T2D on metformin ± SGLT2i, was non-inferior vs. lira and superior vs. pbo in reducing HbA1c, and was superior in reducing BW vs. both lira and pbo. The reduction in HbA1c was significantly better vs. lira when evaluated by the trial product estimand. Disclosure R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. A. Amod: Advisory Panel; Self; Aspen Pharmacare, AstraZeneca, Novartis AG, Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Servier. S.T. Hoff: Employee; Self; Novo Nordisk A/S. T. Kadowaki: Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical, Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Mitsubishi Tanabe Pharma Corporation, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. I. Lingvay: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., MannKind Corporation. Consultant; Self; AstraZeneca, Novo Nordisk Inc., Sanofi, TARGET PharmaSolutions, Valeritas, Inc. Research Support; Self; Merck & Co., Inc., Mylan, Novo Nordisk Inc., Pfizer Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. M.A. Nauck: Advisory Panel; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sun Pharma. K. Pedersen: Employee; Self; Novo Nordisk A/S. T. Saugstrup: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Zealand Pharma A/S. J.J. Meier: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S