Glucagon-Like Peptide-1 Receptor Agonists and Healthy Aging in Older Adults: Balancing Cardiometabolic Benefits with Musculoskeletal Risks

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of obesity and type 2 diabetes and are increasingly being investigated for their potential role in healthy aging. Beyond glycemic control, these agents may influence multiple aging-related pathways, including chronic inflammation, cardiovascular dysfunction, metabolic decline, and frailty. However, concerns have emerged regarding their effects on lean body mass and bone health in older adults.

Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched for clinical trials, observational studies, and meta-analyses evaluating GLP-1RAs in adults aged ≥60 years. Outcomes of interest included body composition, physical function, cardiovascular health, cognitive outcomes, bone mineral density, fracture risk, and markers associated with healthy aging and frailty.

Results: Thirty-one studies met the inclusion criteria. GLP-1RA therapy consistently improved glycemic control, body weight, and cardiometabolic risk factors while reducing visceral adiposity and systemic inflammation. Emerging evidence suggests potential benefits for cardiovascular health and cognitive function. However, several studies reported reductions in lean body mass and decreases in bone mineral density accompanying substantial weight loss, raising concerns regarding sarcopenia, osteoporosis, and fracture risk in vulnerable older populations. These findings suggest that while GLP-1RAs may improve metabolic health, they may also create a bone–muscle trade-off if not accompanied by appropriate supportive interventions.

Conclusions: GLP-1RAs represent a promising therapeutic strategy for addressing obesity and metabolic dysfunction in older adults, with potential implications for healthy aging. Nevertheless, preservation of musculoskeletal health should remain a clinical priority. Future studies should evaluate combined approaches incorporating resistance exercise, adequate protein intake, vitamin D and calcium optimization, and targeted nutritional interventions to maximize benefits while minimizing risks related to sarcopenia and bone loss.