GLP-1 receptor agonist cardiovascular effects appear similar across age groups

An updated meta-analysis of eight randomized, placebo-controlled trials included 71,926 adults with type 2 diabetes or overweight/obesity. GLP-1 receptor agonists were associated with lower rates of major adverse cardiovascular events in participants both younger and older than 65, with no clear evidence that relative effects differed by age.

Eight trials included 71,926 participants.
MACE hazard ratios were 0.81 and 0.84 by age group.
No clear evidence of effect modification by age.
Evidence in adults aged 75 or older was limited.

Researchers searched PubMed and Embase through July 1, 2026, for randomized placebo-controlled trials of GLP-1 receptor agonists in adults with type 2 diabetes or overweight/obesity that reported age-stratified major adverse cardiovascular events (MACE). The meta-analysis included eight trials—SUSTAIN-6, EXSCEL, Harmony Outcomes, PIONEER 6, REWIND, AMPLITUDE-O, SELECT and SOUL—with 71,926 participants. MACE comprised cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.

Pooled hazard ratios for MACE were 0.81 (95% CI 0.69–0.94) among participants younger than 65 and 0.84 (95% CI 0.79–0.90) among those aged 65 or older. The ratio of hazard ratios comparing older with younger participants was 1.03 (95% CI 0.85–1.25), providing no clear evidence of age-related effect modification. Analyses of participants aged 65 to under 75 and 75 or older likewise found no clear differences, but were based on four trials.

The findings suggest similar relative cardiovascular effects across the age groups represented in these trials. Interpretation is limited by substantial between-trial heterogeneity in the age-under-65 analysis and effect-modification analysis, and by relatively few participants aged 75 or older. The results do not establish effects in older adults who are underrepresented in the trials.

In practice

For adults with type 2 diabetes or overweight/obesity represented in the included randomized trials, pooled results showed lower MACE rates with GLP-1 receptor agonists in both participants younger than 65 and those aged 65 or older, with no clear evidence that relative effects differed by age. This supports interpreting age alone as not modifying the relative cardiovascular effect in these trial populations, but does not establish equal benefit for every older patient. Evidence for those aged 75 or older was limited, and between-trial heterogeneity warrants caution.

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Source

Diabetes, Obesity and Metabolism: Cardiovascular Effects of GLP ‐1 Receptor Agonists Across Age Groups: An Updated Meta‐Analysis of Randomized Controlled Trials ↗

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