GLP-1 Therapies Significantly Reduce MACE in Type 2 Diabetes; Efpeglenatide, Albiglutide, Injectable Semaglutide Excel.

Patients with Type 2 Diabetes Mellitus (T2DM) face a significantly elevated risk of cardiovascular disease (CVD), which remains a leading cause of morbidity and mortality. While many antidiabetic medications effectively manage glycemic control, not all demonstrate robust cardiovascular benefits. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a class with established cardioprotective effects, but comparative data on specific agents' impact on major adverse cardiovascular events (MACE) and mortality has been less clear. This network meta-analysis aimed to provide updated, agent-level comparative estimates to guide clinical decision-making.

This study conducted a comprehensive systematic review and frequentist random-effects NMA of 15 randomized controlled trials, involving 97,173 adults with T2DM. Researchers searched PubMed, Cochrane Library, and Scopus through December 2025 for studies evaluating GLP-1-based therapies and reporting time-to-event cardiovascular outcomes. Pairwise meta-analyses and the NMA were performed for key endpoints including all-cause mortality, cardiovascular mortality, MACE, non-fatal myocardial infarction (MI), and non-fatal stroke.

The analysis included 15 trials with a total of 97,173 participants.

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 favored benefit, though most comparisons between agents were not statistically significant. For MACE, efpeglenatide, albiglutide, and injectable semaglutide demonstrated the most favorable comparative profiles among the GLP-1-based therapies. Specifically, albiglutide reduced non-fatal MI compared to placebo. Non-fatal stroke estimates, however, were imprecise across agents, indicating a need for further research in this specific outcome.