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.

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 HFH, SGLT2i exhibited a numerically greater reduction (indirect HR 0.83, 95% CI 0.67-1.03, p = 0.09) that did not reach conventional significance. MI risk was similarly reduced by both classes (indirect HR 1.05, 95% CI 0.83-1.33, p = 0.68). For CV death, the indirect comparison showed no statistically significant difference between classes (HR 0.94, 95% CI 0.76-1.16, p = 0.57), but this estimate is based on limited SGLT2i data (only two trials). The GRADE certainty was low for CV death, primarily due to indirectness (predominantly remote MI populations) and imprecision (wide confidence intervals crossing the line of no effect). Conclusions: In patients with T2DM and a history of MI, indirect evidence suggests that both SGLT2i and GLP-1 RAs reduce MACE, HFH, and recurrent MI, with no statistically significant difference between classes. SGLT2i show a numerically larger HFH reduction, but the difference is not statistically robust. Evidence is largely derived from remote MI, limiting its applicability to the acute post-infarction setting. Treatment choice should be individualized based on patient risk profiles. Dedicated head-to-head trials are urgently needed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261299756, identifier CRD420261299756.