Glucagon-Like peptide-1 receptor agonists (GLP-1-RAs) are increasingly prescribed for type 2 diabetes mellitus and chronic weight management, especially for the rapidly-growing population of older adults. However, older adults are also at heightened risk for sarcopenia and frailty, raising morbidity concerns about GLP-1-RA-induced lean body mass loss. This narrative review summarizes recent studies estimating skeletal muscle mass and/or volume, strength, composition, performance, and acute physiological responses during GLP-1-RA therapy in humans, with particular attention to implications for older adults. Because direct evidence in older adults is scarce, this review primarily synthesizes data from general adult populations and reasonably extrapolates implications for older adults. Most studies found that GLP-1-RA therapy was associated with a loss of skeletal muscle mass, accounting for up to 8.5% to 24.5% of total weight loss. Studies assessing muscle quality mostly saw improved muscle quality following GLP-1-RA therapy due to higher muscle density and decreased fat content. Studies measuring muscle strength generally found no significant change. However, from 21 included studies, only four studies specifically examined the older adult population, being methodologically heterogeneous and difficult to compare. The limited published literature in older adults provides insufficient evidence to determine age-related vulnerability to skeletal muscle loss while on GLP-1-RA and the potential clinical complications of resultant frailty; additional research in older adult populations is needed. Provisional considerations for preserving muscle mass during GLP-1-RA therapy are discussed, with particular relevance to older adults. This review demonstrates that the degree of skeletal muscle loss is variable but can account for a meaningful fraction of weight lost during therapy. Providers should consider these potential effects when prescribing GLP-1-RAs, especially in older adults at risk for frailty.
