Risk of protein intake deficiency during treatment with GLP-1 and GIP/GLP-1 receptor agonists: considerations for secondary sarcopenia.

Abstract

Sarcopenia, characterized by the age-related decline in muscle mass and strength, increases the risk of falls, fractures, disability, and mortality. Type 2 diabetes and obesity frequently coexist with sarcopenia, contributing to the growing clinical challenge of sarcopenic obesity. Incretin-based therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and dual gastric inhibitory polypeptide (GIP)/GLP-1 receptor agonists, induce substantial weight loss through reduced calorie intake and are increasingly prescribed to older adults. However, weight reduction driven by appetite suppression may also decrease absolute protein intake, potentially compromising muscle health in individuals already vulnerable to anabolic resistance. This review examines the available evidence on changes in dietary protein intake during incretin-based therapy and their implications for muscle mass and functional preservation in older adults. Randomized trials suggest that liraglutide generally maintains protein intake as a proportion of total energy (approximately 13.9-17.5%), yet reductions in absolute protein intake may occur due to overall caloric restriction, particularly with more potent appetite suppression. Importantly, even when proportional intake is preserved, reductions in total energy intake may lower absolute protein consumption below levels required to adequately stimulate muscle protein synthesis in older adults. Comprehensive data on dietary intake remain limited, and few studies have systematically evaluated whether such changes translate into clinically meaningful declines in muscle mass, strength, or physical performance. Longer-term trials incorporating detailed dietary assessment, body composition analysis, and functional outcomes are needed to clarify the impact of incretin-based therapies on protein adequacy and muscle health in older adults. A clearer understanding of these interactions is essential to optimize weight management strategies while minimizing the risk of secondary sarcopenia.