Current evidence and emerging therapeutic strategies for non-exercise interventions in sarcopenia associated with...

Skeletal muscle provides the foundation for respiration and physical activity and plays an essential role in human survival. Chronic obstructive pulmonary disease (COPD)-associated sarcopenia is highly prevalent and significantly affects exercise tolerance, quality of life, and long-term prognosis. Unlike irreversible airway damage, skeletal muscle dysfunction remains potentially treatable. Pulmonary rehabilitation remains the cornerstone intervention; however, its application is substantially limited during acute exacerbations and in patients with severe disease. This review aims to summarize current evidence on non-exercise interventions for COPD-associated sarcopenia.

To retrieve literature related to non-exercise therapeutic strategies for COPD-associated sarcopenia, a keyword search was performed, which covered PubMed and Web of Science databases for publications from January 1, 2009 to March 31, 2026.

This review categorizes non-exercise interventions for COPD-associated sarcopenia into three evidence tiers. Category 1 (clinical evidence from COPD studies): butyrate improves handgrip strength, gait speed, and short physical performance battery (SPPB); whey protein with vitamin D enhances muscle strength and performance; heliox increases exercise endurance; RJx-01 is currently under phase II investigation with results pending; myostatin inhibitors increase lean mass without functional gain. Category 2 (preclinical evidence from COPD models): hydrogen therapy, glycyrrhizin, and Jinshui Liujun decoction mitigate muscle wasting via anti-oxidative, anti-inflammatory, and multi-target metabolic pathways. Category 3 (translational strategies from other wasting disorders): selective androgen receptor modulators (SARMs), growth differentiation factor-15 (GDF-15) antibody, and cell/gene therapy, all of which have demonstrated efficacy in cancer cachexia or age-related sarcopenia, represent promising directions for future research in COPD.

Despite the current paucity of direct clinical evidence for non-exercise therapies in COPD-related sarcopenia, intensive ongoing investigations are catalyzing a pivotal shift in the field. By translating preclinical breakthroughs into targeted interventions, these advancements are paving the way for a new era of multifaceted therapeutic strategies, ultimately aiming to mitigate muscle dysfunction and improve outcomes in patients with COPD.