Impact of GLP-1 receptor agonists on sarcopenia in older adults

The National Institute on Aging awarded Arizona State University $436,228 on June 1, 2026, under the Aging Research program (CFDA 93.866) to evaluate the impact of glucagon-like peptide-1 receptor agonists on sarcopenia in older adults.

The research project will measure muscle mass and the mechanisms regulating muscle mass—including muscle protein synthesis and breakdown—using stable isotope tracer methodologies in older patients before and six months after GLP-1 RA treatment. The study will assess changes in muscle fiber types, mitochondrial function, and muscle quality using isolated muscle fibers, mitochondrial respiration assays, and strength measurements from dynamometry adjusted for muscle mass. The project addresses a critical knowledge gap regarding GLP-1 RA effects on skeletal muscle health in older adults, as current evidence linking these agents to muscle loss relies largely on extrapolated data from younger populations that measure lean body mass rather than direct muscle mass assessment.

Performance runs from June 1, 2026, through May 31, 2028, with work performed in Tempe, Arizona. The award is structured as a Project Grant, classified as assistance funding.

Mayo Clinic Arizona serves as a sub-recipient, performing work aligned with the same research objectives under sub-award R21AG098538-ASUB00002308, awarded August 13, 2026.

Abstract

The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1 RAS) among older adults highlights the urgent need to investigate their potential impact on skeletal muscle health, as emerging concerns suggest they may accelerate muscle loss and worsen sarcopenia-the age-related decline in muscle mass and function. Current evidence linking GLP-1 RAS to muscle loss is largely based on extrapolated data from studies in younger individuals, which often measure lean body mass rather than directly assessing muscle mass. This critical knowledge GAP leaves older adults, who are already at a higher risk for sarcopenia, particularly vulnerable to potential muscle-related complications from GLP-1 RA therapy. This project will evaluate the effects of GLP-1 RA pharmacotherapy on muscle health in older patients before and six months after treatment. Specifically, we will measure muscle mass and investigate the underlying processes that regulate muscle mass (i.e., muscle protein synthesis and breakdown) using stable isotope tracer methodologies. Additionally, we will assess changes in muscle fiber types, mitochondrial function, and overall muscle quality/functional capacity. Single muscle fibers will be isolated from collected muscle samples to determine fiber type distribution. Mitochondrial function will be assessed using mitochondrial respiration assays in isolated mitochondria, while muscle quality will be evaluated based on strength measurements from dynamometry, adjusted for muscle mass. While concerns exist about GLP-1 RA pharmacotherapy and potential muscle loss, emerging evidence suggests IT may have beneficial effects on muscle quantity and quality in older adults. This project will generate foundational data essential for understanding its specific impact on muscle health in this population. The findings will help fill a critical knowledge GAP and provide key data for larger, hypothesis-driven clinical trials, ultimately advancing our understanding of the complex relationship between GLP-1 RA pharmacotherapy and muscle health in older adults.