Methods and aims

Despite the growing body of evidence on GLP-1-RAs and body composition, significant gaps remain in the literature. Most existing reviews are difficult to interpret due to the confounding effects of different measurement methods and amalgamation of human and animal studies [32]. For instance, many studies use lean mass as a proxy for muscle mass, making them difficult to compare with studies that estimate muscle mass with other methods. Studies also differ in the dose titration of the GLP-1-RA medication used, making it essential to analyze this factor as a source of variability. Critically, older adults are severely underrepresented in clinical trials of GLP-1-RAs. This underrepresentation currently limits the ability to make informed treatment decisions for a population at high risk of sarcopenia and functional decline. Therefore, the goal of this narrative review is to summarize the most recent literature on GLP-1-RAs and muscle health in adult populations, with particular attention to implications for older adults. By doing so, this review aims to clarify the currently scattered evidence on the effects of GLP-1-RAs on muscle, thereby providing provisional considerations for maintaining muscle health during GLP-1-RA therapy, with particular relevance to older adults.

As a narrative review, this work does not provide pooled estimates or draw causal inference, but aims to identify patterns, gaps, and clinically relevant signals within heterogeneous literature. A literature search was conducted in January 2026 using PubMed and Google Scholar. The search strategy combined three conceptual domains: 1) GLP-1-RA-related terms (e.g. “GLP-1″, “GLP-1 receptor agonist”, “semaglutide”, “liraglutide”, “tirzepatide”), 2) muscle-related terms (e.g. “muscle mass”, “muscle volume”, “muscle loss”, “skeletal muscle”), and 3) contextual terms (e.g. “body composition”, “older adults”, and “sarcopenia”). In order to maximize article retrieval, various combinations of terms from each domain were used. For example, representative PubMed search strings included (“GLP-1″ OR “GLP-1 receptor agonist” OR “semaglutide” OR “liraglutide” OR “tirzepatide”) AND (“muscle mass” OR “muscle volume” OR “muscle loss” OR “skeletal muscle”) AND (“body composition” OR “older adults” OR “sarcopenia”). The search was not restricted by language. Reference lists of retrieved articles were also hand-searched to identify additional studies. The authors screened article titles and abstracts for relevance, followed by full-text review to determine study eligibility.

Articles were included if they: 1) were published within the last seven years (2020–2026), 2) reported at least one outcome in one or more of the following four domains: (a) muscle quantity via estimation of skeletal muscle mass or volume (i.e. BIA, MRT, CT, or administrative diagnosis codes), (b) muscle composition or quality (i.e. intramuscular fat content, muscle density or attenuation, or muscle quality indices), (c) muscle strength or physical performance (i.e. handgrip strength, gait speed, chair rise time, six-minute walk distance), or (d) acute mechanistic responses to GLP-1 or GLP-1-RA exposure (i.e. muscle protein synthesis, microvascular blood flow), and 3) were conducted in human participants. Studies were excluded if they 1) were published before 2020, 2) were conducted in animal models, 3) only reported lean body mass, and 4) did not report original data. By excluding animal studies and studies using proxies for skeletal muscle mass (i.e. lean mass), this review aims to minimize confounders and synthesize studies with direct relevance to researchers and clinicians. We included human studies reporting estimated or proxy measures of skeletal muscle quantity (e.g. BIA, MRI/CT volumes, clinical diagnosis codes), muscle composition or density, muscle strength or performance (e.g. handgrip strength, six-minute walk), and acute physiological responses to GLP-1 or GLP-1-RA exposure in order to capture the full breadth of available evidence on the effects of GLP-1 and GLP-1-RAs on skeletal muscle. Furthermore, to our knowledge, this is the first review to separate studies of general adults from older adults to allow for potential comparison.