Cardiovascular outcome differences between individual glucagon-like peptide-1 (GLP-1)-based therapies remain clinically relevant in Type 2 diabetes mellitus (T2DM), particularly as use of these agents continues to expand in patients with elevated cardiovascular risk. A systematic review and network meta-analysis published in Diabetes, Obesity and Metabolism compared cardiovascular outcomes across GLP-1-based therapies using data from 15 randomized controlled trials involving 97,173 participants.
The analysis included adults with T2DM enrolled in placebo-controlled cardiovascular outcome trials. Pairwise meta-analyses evaluated class-level effects, while a frequentist random-effects network meta-analysis compared outcomes between individual agents. The evaluated endpoints included all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), non-fatal myocardial infarction (MI), and non-fatal stroke.
Findings
- Pairwise placebo-controlled analyses showed significant reductions in all-cause mortality, cardiovascular mortality, and MACE with GLP-1-based therapies overall.
- Efpeglenatide, albiglutide, and injectable semaglutide showed the most favorable comparative profiles for MACE in the network meta-analysis.
- Mortality estimates favored benefit for several agents, although most between-agent comparisons were not statistically significant.
- Albiglutide reduced non-fatal MI risk versus placebo, while estimates for non-fatal stroke remained imprecise across therapies.
The analysis supported an overall favorable cardiovascular profile for GLP-1-based therapies in adults with T2DM. Differences between individual agents appeared more evident for MACE than for mortality outcomes. The findings also suggested that comparative cardiovascular effects within the GLP-1 class may not be uniform across all endpoints.
