SGLT2 inhibitors versus GLP-1 receptor agonists for major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Abstract
BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to reduce cardiovascular risk, but direct comparison is limited. Objective: Compare the effects of SGLT2 inhibitors and GLP-1 receptor agonist on major adverse cardiovascular events (MACE) in adults with T2DM using randomized controlled trials and indirect comparisons. METHODS: A systematic search of PubMed, Scopus, CENTRAL, and Google Scholar was conducted through October 20, 2025, following PRISMA 2020 guidelines. The protocol was registered with PROSPERO (CRD420251168485). We included randomized controlled trials (RCTs) of SGLT2i or GLP-1RA versus placebo in adults with T2DM that reported cardiovascular or renal outcomes. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using the generic inverse variance method with a random-effects model. An indirect treatment comparison was performed using the Bucher method. Risk of bias was assessed with the Cochrane RoB 1 tool. RESULTS: We reviewed twelve trials involving 99,261 individuals (5 SGLT2i, 7 GLP-1RA). Compared to placebo, SGLT2i significantly reduced MACE (HR 0.89, 95% CI 0.84–0.95; p = 0.0003), as did GLP-1RA (HR 0.82, 95% CI 0.78–0.87; p < 0.00001). The indirect comparison indicated a nominally greater MACE reduction with GLP-1RA (HR 1.09, 95% CI…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 99,261 participants or records.
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