Efficacy of GLP-1 receptor agonists among older adults: a meta-analysis of cardio-kidney outcome trials.

BACKGROUND: Older adults face high cardiovascular (CV) and kidney risk but may be underrepresented in randomized controlled trials (RCTs). While GLP-1RAs have been shown to provide CV and kidney benefits, estimates for efficacy and safety endpoints among older adults remain less certain. This meta-analysis assesses their impact on CV and kidney outcomes. METHODS: This systematic review and meta-analysis followed PRISMA guidelines. Outcomes included composite kidney outcome, 3-point major adverse cardiovascular events (3p-MACE), CV death, stroke, myocardial infarction (MI), and hospitalization for heart failure (HHF). Hazard ratios (HRs) were pooled using a random-effects model. Subgroup analysis was performed between older adults (≥65 years) and younger adults (<65 years). RESULTS: Eleven RCTs with 85,373 participants were included, out of which 44,013 (51.6 %) were older adults. Among older adults, GLP-1RAs significantly reduced the composite kidney outcome by 22 % (HR: 0.78; 95 % CI: 0.70-0.87; p < 0.001), 3-p MACE by 15 % (HR: 0.85; 95 % CI: 0.78-0.94; p = 0.001), and CV death by 15 % (HR: 0.85; 95 % CI: 0.72-1.00; p = 0.05). Nonsignificant trends were observed for stroke (HR: 0.86; 95 % CI: 0.74-1.01; p = 0.06), MI (HR: 0.86; 95 % CI: 0.70-1.05; p = 0.14), and HHF (HR: 0.88; 95 % CI: 0.73-1.06; p = 0.17). These efficacy estimates among older adults were consistent with those among younger adults, with statistical evidence of heterogeneity (all p for interaction > 0.2). CONCLUSIONS: GLP-1RAs significantly reduce MACE, CV death, and kidney events in older adults, supporting their use in this population. While benefits on stroke, MI, and HHF were less conclusive, trends favor GLP-1RA use.

Duke Scholars

Author Stephen Greene Medicine, Cardiology