Efficacy of GLP-1 receptor agonists among older adults: a meta-analysis of cardio-kidney outcome trials
Abstract
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.
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Individuals with cognitive impairments, mobility limitations, or on polypharmacy regimens may experience difficulties with injectable GLP-1 receptor agonist therapies.
“For example, individuals with cognitive impairments, mobility limitations, or on polypharmacy regimens may experience difficulties with injectable therapies, which are a common form of administration for GLP-1 Ras [48].”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [48]
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- Authors
- Waqas, S. A., Ali, D., Afridi, M. K., Siddiqui, H. F., Nazir, A., Greene, S. J., & Khan, M. S.
- Affiliations
- Dow University of Health Sciences (PK)
- University of Louisville (US)
- Duke University (US)
- Baylor Scott & White Medical Center - Temple (US)
- Corresponding author
- Waqas, Saad Ahmed
- Ali, Dua
- ORCID
- Venue
- Archives of Gerontology and Geriatrics
- Publisher
- Elsevier BV
- Published
- 2025-11
- Volume
- 138
- Pages
- 105981
- ISSN
- 0167-4943 (ISSN-L)
- OpenAlex
- W4413137945
- Cited by
- 11
- References
- 53
- Citations by year
- 2026: 9 · 2025: 2
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Archives of Gerontology and Geriatrics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- GLP-1 receptor agonists, older adults, cardiovascular outcomes, renal outcomes, major adverse cardiovascular events, cardiovascular mortality, stroke, myocardial infarction, heart failure hospitalization, subgroup analysis, type 2 diabetes treatment, drug safety in elderly, underrepresentation in clinical trials, subgroup heterogeneity
- MeSH terms
- Glucagon-Like Peptide-1 Receptor Agonists, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Heart Failure, Humans, Hypoglycemic Agents, Randomized Controlled Trials as Topic
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