The Impact of GLP-1-Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta-Analysis.

AIMS: To provide updated agent-level comparative estimates of GLP-1-based therapies for cardiovascular outcomes in adults with Type 2 diabetes mellitus (T2DM) using a hazard ratio (HR)-based systematic review and network meta-analysis (NMA).

METHODS

PubMed, Cochrane Library and Scopus were searched through December 2025 for randomized controlled trials evaluating GLP-1-based therapies in adults with T2DM and reporting time-to-event cardiovascular outcomes. Pairwise meta-analyses and a frequentist random-effects NMA were performed for all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), non-fatal myocardial infarction (MI) and non-fatal stroke.

RESULTS

Fifteen trials involving 97,173 participants were included. In pairwise placebo-controlled analyses, GLP-1-based therapies significantly reduced all-cause mortality, cardiovascular mortality and MACE. In the NMA, mortality estimates for several agents favoured benefit, although most comparisons were not statistically significant. For MACE, efpeglenatide, albiglutide and injectable semaglutide showed the most favourable comparative profiles. Albiglutide reduced non-fatal MI versus placebo, whereas non-fatal stroke estimates were imprecise.

CONCLUSIONS

GLP-1-based therapies were associated with an overall favourable cardiovascular profile in T2DM. Pairwise analyses supported class-level benefit, whereas between-agent differences were more evident for MACE than for mortality outcomes in the NMA.