Meta-analysis
Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists
- Systematic review and meta-analysis of randomised trials
- prespecified subgroups
- GRADE
- trial sequential analysis
Authors' conclusion
GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased gastrointestinal and gallbladder risks.
Study context
- Population
- Diverse populations in RCTs of GLP-1 RAs (subgroups by DM, kidney function, obesity, HF)
- Participants
- 99,599 participants · 21 trials
- Comparison
- GLP-1 RAs vs controls or placebo
- Outcome
- Mortality (all-cause and cardiovascular (CV)), trial-defined major adverse cardiovascular events (MACE) and serious adverse events
- Follow-up
- Mean 2.4 years
Pooled result
As reported in the abstract
GLP-1 RAs vs ControlsIncidence rate ratio (95% CI)
all-cause death; NNT = 121
0.88(0.84–0.92)
CV death; NNT = 170
0.87(0.81–0.92)
MACE; NNT = 66
0.87(0.83–0.91)
Further pooled results
MI, acute kidney failure, HF, infections
- MI reduced
- −15%
- Acute kidney failure reduced
- −9%
- HF reduced
- −15%
- Infections reduced
- −10%
Stroke
- No difference in stroke between groups
Safety
Serious adverse events
- Serious adverse events reduced
- −9%
Gastrointestinal and gallbladder disorders
- Gastrointestinal disorders increased
- +63%
- Gallbladder disorders increased
- +26%
Pancreatitis, neoplasm
- No differences in pancreatitis or neoplasm between groups
Original publication
Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists. J Am Coll Cardiol. Published 27 August 2025. doi:10.1016/j.jacc.2025.08.027
Summarised from the published abstract; every number is checked against it