GLP-1 receptor agonists lowered MACE in adults aged under 65 and 65 or older

The study

This is a meta-analysis of randomised controlled trials, published in Diabetes, Obesity & Metabolism. The authors asked whether the cardiovascular effects of GLP-1 receptor agonists (GLP-1RAs) differ by age.

They searched PubMed and Embase up to 1 July 2026. They included placebo-controlled GLP-1RA trials in adults with type 2 diabetes or overweight/obesity that reported age-stratified major adverse cardiovascular events (MACE). MACE was defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.

Hazard ratios (HRs) were pooled separately for participants aged under 65 and 65 years or older, using random-effects models. To test whether age changed the effect, the authors pooled each trial's ratio of HRs (RHR) for 65 or older versus under 65. Where trials reported them, three age groups were also examined: under 65, 65 to under 75, and 75 or older.

What they found

Eight trials were included: SUSTAIN-6, EXSCEL, Harmony Outcomes, PIONEER 6, REWIND, AMPLITUDE-O, SELECT and SOUL. Together they had 71 926 participants.

• Under 65 years: pooled HR for MACE 0.81 (95% CI 0.69-0.94; I2 = 64.1%).
• 65 years or older: pooled HR 0.84 (95% CI 0.79-0.90; I2 = 0.0%).
• Pooled RHR for effect modification: 1.03 (95% CI 0.85-1.25). The authors found no clear evidence that age modified the effect. Between-trial heterogeneity was high (I2 = 59.3%).

In the three-age-group analysis, there was again no clear evidence of effect modification for 65 to under 75 or for 75 or older, each compared with under 65. Only four trials had these data, and the group aged 75 or older was relatively small.

How much weight to give it

This is a meta-analysis of randomised placebo-controlled trials, so the pooled results rest on randomised comparisons. The authors concluded that GLP-1RAs lowered MACE in the age groups examined, with no clear evidence that relative effects differed by age.

"No clear evidence of a difference" is not proof that the effects are the same. The confidence interval for the RHR (0.85-1.25) leaves room for some difference in either direction.

Several limits come from the abstract itself. Between-trial heterogeneity was high for the under-65 HR (I2 = 64.1%) and for the RHR (I2 = 59.3%). Only four trials reported three age groups, and the group aged 75 or older was relatively small, so the estimates for the oldest group are the least certain. The included trials enrolled adults with type 2 diabetes or overweight/obesity, and the conclusions apply across these trial populations.

The abstract does not report funding, risk-of-bias assessment, or follow-up length. It also does not give absolute risks, so it cannot show how much benefit older people gain in absolute terms.

For your clinic

Across the included trial populations, GLP-1RAs lowered MACE in both the under-65 and 65-or-older groups, with no clear evidence that relative cardiovascular effects differed by age. Data for people aged 75 or older came from only four trials and a relatively small group.

The abstract says nothing about safety or tolerability by age, so this paper does not settle those questions. Read the full paper, the individual trial reports and current guidelines before changing how you choose treatment for older patients. Treatment decisions should stay individual.