Abstract
OBJECTIVE Efficacy and safety of the GLP-1 analog, oral semaglutide, and the SGLT-2 inhibitor, empagliflozin, were compared in patients with type 2 diabetes uncontrolled on metformin.
RESEARCH DESIGN AND METHODS Patients were randomized to once-daily open-label treatment with oral semaglutide 14 mg (n = 412) or empagliflozin 25 mg (n = 410) in a 52-week trial. Key endpoints were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands addressed 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 patients.
RESULTS Four-hundred patients (97.1%) in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial. Oral semaglutide provided superior reductions in HbA1c versus empagliflozin at week 26 (treatment policy: –1.3% vs. –0.9% [–14 vs. –9 mmol/mol]; estimated treatment difference [ETD]: –0.4%, 95% CI –0.6, –0.3 [–5 mmol/mol, 95% CI –6, –3]; P< 0.0001). The treatment difference in HbA1c significantly favored oral semaglutide at week 26 for the trial product estimand (–1.4% vs. –0.9% [–15 vs. –9 mmol/mol]; ETD: –0.5%, 95% CI –0.7, –0.4 [–6 mmol/mol, 95% CI –7, –5]; P< 0.0001), and at week 52 for both estimands (P< 0.0001). Superior weight loss was not confirmed at week 26 (treatment policy), but oral semaglutide was significantly better than empagliflozin at week 52 (trial product: −4.7 vs. −3.8 kg; P = 0.0114). Gastrointestinal adverse events were more common with oral semaglutide.
CONCLUSIONS Oral semaglutide was superior to empagliflozin in reducing HbA1c but not body weight at 26 weeks in patients with type 2 diabetes uncontrolled on metformin. At week 52, HbA1c and body weight (trial product estimand) were significantly reduced versus empagliflozin. Oral semaglutide was well tolerated within the established safety profile of GLP-1 receptor agonists.
Footnotes
↵* A complete list of investigators in the Peptide Innovation for Early Diabetes Treatment 2 trial (PIONEER 2) is provided in the Supplemental Appendix.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc19-0883/-/DC1.
- Received May 2, 2019.
- Accepted September 12, 2019.
- © 2019 by the American Diabetes Association.
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