Cardiovascular Effects of
GLP
‐1 Receptor Agonists Across Age Groups: An Updated Meta‐Analysis of Randomized Controlled Trials
Ai Fujii, Masashi Hasebe, Kengo Furuichi, Daisuke Yabe, Satoshi Yoshiji ABSTRACT
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; I 2 = 64.1%) and 0.84 (95% CI 0.79–0.90; I 2 = 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 ( I 2 = 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.