Oral semaglutide (sema) is the first oral GLP-1 receptor agonist (RA). Flexible dose adjustment of oral sema (3, 7, and 14 mg) once daily (N=253) was tested vs. sitagliptin (sita, 100 mg; N=251) in a 52-week (week), randomized, open-label phase 3a trial in patients (pts) with T2D uncontrolled on 1-2 oral glucose-lowering drugs (NCT02849080). Oral sema dose could be adjusted every 8 weeks based on HbA1c (escalated if ≥7.0%) and tolerability. Endpoints at week 52: HbA1c <7.0% (primary); body weight change (secondary). Two scientific questions were addressed by 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. At week 52, 9.0, 30.2 and 59.4% of oral sema pts were on 3, 7 and 14 mg, respectively. Oral sema was superior to sita for HbA1c <7.0% and weight loss, and gave a significantly better reduction in HbA1c at week 52 (Table). Fewer pts on oral sema needed rescue medication (3 vs. 16%). Adverse events (AEs) were more common with oral sema (78 vs. 69%), mostly mild/moderate and transient nausea (21 vs. 2%). Trial product discontinuation due to AEs (mostly gastrointestinal) was higher with oral sema (9 vs. 3%).
In conclusion, flexible dose adjustment with oral sema provided superior glycemic control and weight loss at week 52 vs. sita, and was well tolerated with safety consistent with the GLP-1RA class.
J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. Y. Cho: Consultant; Self; Hanmi Pharm. Co., Ltd. Research Support; Self; AstraZeneca, Sanofi-Aventis. E. Christiansen: None. C.L. Hertz: Employee; Self; Novo Nordisk A/S. A. Mertens: None. S.O. Wallenstein: None. T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor Limited, AstraZeneca, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Novo Nordisk A/S.
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