Cardiovascular Effects of GLP-1 Receptor Agonists Across Age Groups: An Updated Meta-Analysis of Randomized Controlled Trials.

Aims

To evaluate whether cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) differ by age.

Materials And Methods

PubMed and Embase were searched to 1 July 2026 for randomized placebo-controlled GLP-1RA trials in adults with type 2 diabetes or overweight/obesity reporting age-stratified major adverse cardiovascular events (MACE; a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). Hazard ratios (HRs) for participants aged < 65 and ≥ 65 years were pooled using random-effects models with restricted maximum likelihood estimation and Hartung-Knapp adjustment. Effect modification was assessed by pooling trial-specific ratios of HRs (RHRs) for ≥ 65 versus < 65 years. Where reported, effects were assessed across < 65, 65 to < 75 and ≥ 75 years.

Results

Eight trials (SUSTAIN-6, EXSCEL, Harmony Outcomes, PIONEER 6, REWIND, AMPLITUDE-O, SELECT and SOUL) comprising 71 926 participants were included. GLP-1RAs reduced MACE at < 65 years and ≥ 65 years, with pooled HRs of 0.81 (95% CI 0.69-0.94; I2 = 64.1%) and 0.84 (95% CI 0.79-0.90; I2 = 0.0%), respectively. The pooled RHR showed no clear evidence of effect modification (1.03, 95% CI 0.85-1.25), although between-trial heterogeneity was high (I2 = 59.3%). Among trials reporting three age strata, RHRs showed no clear evidence of effect modification for 65 to < 75 or ≥ 75 years versus < 65 years, but data were available from only four trials, and the ≥ 75-year group was relatively small.

Conclusions

Across the included trial populations, GLP-1RAs lowered MACE in the age groups examined, with no clear evidence that relative cardiovascular effects differed by age.