The GLP-1 analog oral semaglutide (sema) 14 mg once daily (QD, N=411) was compared with the SGLT2i empagliflozin (empa) 25 mg QD (N=410) in patients (pts) with T2D uncontrolled on metformin in a 52-week randomized, open-label trial (NCT02863328). Endpoints included change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two scientific questions were addressed through defining two estimands: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized pts. Oral sema was superior to empa at reducing HbA1c at week 26; the difference was also significant at week 52 (Table). More patients achieved HbA1c <7.0% with oral sema. Weight loss with oral sema was not superior at week 26, but significantly greater at week 52 (trial product estimand). Proportions of adverse events (AEs) were similar between oral sema (70.5%) and empa (69.2%). The most frequent AEs with oral sema were mild/moderate gastrointestinal events. Premature trial product discontinuations due to AEs were 11% (oral sema) vs. 4% (empa).
In conclusion, oral sema provided superior reductions in HbA1c but not body weight at week 26, and significant reductions in HbA1c and body weight (trial product estimand) at week 52 vs. empa. Oral sema was well tolerated within the established safety profile of GLP-1RAs.
E. Montanya: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Servier. Consultant; Self; Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation. Employee; Spouse/Partner; Almirall, S.A. Research Support; Self; Menarini Group. Speaker's Bureau; Self; Novo Nordisk A/S. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck & Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. L.H. Canani: Research Support; Self; Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. C. Deerochanawong: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. J. Gumprecht: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Bioton, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi-Aventis, Servier. S. Lindberg: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. 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. A.L. Søndergaard: Employee; Spouse/Partner; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M. Treppendahl: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. H.W. Rodbard: Advisory Panel; Self; Bayer US, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Spouse/Partner; Eli Lilly and Company. Consultant; Self; Gan & Lee Pharmaceuticals. Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Merck & Co., Inc., Novo Nordisk Inc.
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