Efficacy of once-weekly semaglutide vs empagliflozin added to metformin in type 2 diabetes: Patient-level meta-analysis

Ildiko Lingvay, Matthew S. Capehorn, Andrei Mircea Catarig, Pierre Johansen, Jack Lawson, Anna Sandberg, Robert Shaw, Abby Paine

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Context: No head-to-head trials have directly compared once-weekly (OW) semaglutide, a human glucagon-like peptide-1 analog, with empagliflozin, a sodium–glucose co-transporter-2 inhibitor, in type 2 diabetes (T2D). Objective: We indirectly compared the efficacy of OW semaglutide 1 mg vs once-daily (OD) empagliflozin 25 mg in patients with T2D inadequately controlled on metformin monotherapy, using individual patient data (IPD) and meta-regression methodology. Design, Setting, Participants, and Interventions: IPD for patients with T2D receiving metformin monotherapy and randomized to OW semaglutide 1 mg (SUSTAIN 2, 3, 8 trials), or to OD empagliflozin 25 mg (PIONEER 2 trial) were included. Meta-regression analyses were adjusted for potential prognostic factors and effect modifiers. Main Outcome Measures: The primary efficacy outcomes were change from baseline to end-of-treatment (~1 year) in HbA1c (%-point) and body weight (kg). Responder outcomes and other clinically relevant efficacy measures were analyzed. Results: Baseline characteristics were similar between OW semaglutide (n = 995) and empagliflozin (n = 410). Our analyses showed that OW semaglutide significantly reduced mean HbA1c and body weight vs empagliflozin (estimated treatment difference: −0.61%-point [95% confidence interval (CI): −0.72; −0.49] and −1.65 kg [95% CI: −2.22; −1.08], respectively; both P < 0.0001). Complementary analyses supported the robustness of these results. A significantly greater proportion of patients on OW semaglutide vs empagliflozin also achieved HbA1c targets and weight-loss responses. Conclusions: This indirect comparison suggests that OW semaglutide 1 mg provides superior reductions in HbA1c and body weight vs OD empagliflozin 25 mg in patients withT2D when added to metformin monotherapy.

Original languageEnglish (US)
Article numberdgaa577
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
StatePublished - Dec 1 2020


  • GLP-1 receptor agonist
  • Indirect comparison
  • Individual patient data
  • SGLT-2 inhibitor
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Efficacy of once-weekly semaglutide vs empagliflozin added to metformin in type 2 diabetes: Patient-level meta-analysis'. Together they form a unique fingerprint.

Cite this