Cardiovascular outcomes of SGLT2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes and a history of myocardial infarction: a systematic review and network meta-analysis of randomized controlled trials
Abstract
Background: Patients with type 2 diabetes (T2DM) and a history of myocardial infarction (MI) face a high risk of recurrent cardiovascular events. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk, but no head-to-head trials exist. We performed a systematic review and network meta-analysis (NMA) to indirectly compare their cardiovascular efficacy in this high-risk population.
Methods: Randomized controlled trials (RCTs) published up to February 1, 2026, were systematically searched and evaluated. The primary outcome was major adverse cardiovascular events (MACE); secondary outcomes included hospitalization for heart failure (HFH), MI, and cardiovascular death (CV death). A frequentist NMA was used as the primary comparative analysis, complemented by Bucher interaction tests as sensitivity analyses. Evidence certainty was assessed with GRADE.
Results: Eleven RCTs were included; after exclusion of overlapping populations, the final analyses comprised 7 studies for MACE (2 SGLT2i, 5 GLP-1 RA), 6 for HFH (2 SGLT2i, 4 GLP-1 RA), 4 for MI (1 SGLT2i, 3 GLP-1 RA), and 6 for CV death (2 SGLT2i, 4 GLP-1 RA). Both drug classes significantly reduced MACE compared to placebo (SGLT2i HR 0.87, 95% CI 0.77-0.97; GLP-1 RA HR 0.83, 95% CI 0.77-0.89). The NMA indirect comparison for MACE yielded an HR of 1.05 (95% CI 0.92-1.20, p = 0.44), indicating no statistically significant difference between classes. For…
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