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

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 HbA_1c (%-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 HbA_1c 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 HbA_1c targets and weight-loss responses. Conclusions: This indirect comparison suggests that OW semaglutide 1 mg provides superior reductions in HbA_1c and body weight vs OD empagliflozin 25 mg in patients withT2D when added to metformin monotherapy.