Pharmacologic Treatments for the Preservation of Lean Body Mass During Weight Loss.
This narrative review examines the problem of lean body mass (LBM) loss associated with weight loss, with particular focus on incretin-based therapies such as GLP-1 receptor agonists (e.g., semaglutide) and dual GIP/GLP-1 receptor agonists (e.g., tirzepatide). The authors queried PubMed, Medline, and Scopus for randomized controlled trials and Phase II/III trials related to obesity, muscle loss, and lean mass preservation, excluding animal studies. The review outlines the physiological mechanisms driving muscle loss during caloric deficit—including reduced anabolic signaling, increased protein catabolism, and hormonal changes—and surveys pharmacological agents under investigation to counteract these effects. Key drug classes discussed include bimagrumab (an activin receptor antagonist targeting the myostatin pathway), tesamorelin (a growth hormone-releasing hormone agonist), and enobosarm (a selective androgen receptor modulator). The authors note that while incretin-based therapies represent a major advance in obesity management, the accompanying loss of muscle mass is a clinically meaningful concern. Most agents targeting LBM preservation are in early research phases. Limitations include reliance on narrative rather than systematic methodology, potential selection bias in study inclusion, and the rapidly evolving evidence base in this area.
Why this grade: This is a narrative review synthesizing existing RCTs and phase II/III trials rather than generating new primary human data, so it is graded as review-level evidence.
Introduction : Overweight and obesity are becoming increasingly prevalent. Incretin-based obesity treatments-glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonists (GIP/GLP-1 RAs or dual agonists)-are a major stride in the evolution of obesity management. However, like weight loss with other means, they are associated with an inadvertent significant loss of lean body mass, including muscle. This has led to a resurgence in research for the preservation of lean body mass, the loss of which occurs with weight loss. The purpose of this narrative review is to discuss the mechanisms involved with lean body loss and capture the research landscape of the different classes of pharmacological agents being developed to address this problem. Methodology : We queried PubMed, Medline, and Scopus for randomized controlled trials and phase II or phase III trials using key words to capture the breath of this topic-obesity, weight loss, muscle loss, lean mass, and muscle preservation. Animal studies were excluded. We analyzed the studies conducted to date. Results : Weight loss, regardless of the method used to achieve it, is inadvertently accompanied by lean body mass loss, to varying degrees. There are several mechanisms that govern the loss of lean body mass and, more specifically, the loss of muscle mass; as such, several classes of medications have been explored, targeting different pathways and receptors-including bimagrumab (activin receptor agonist), tesamorelin (growth hormone releasing hormone agonists), and enobosarm (selective androgen receptor modulator). Most of these drugs are in the early phases of research development, but some show great promise. Conclusion : This narrative review attempts to detail the physiology of muscle mass loss when accompanied by weight loss and identify pharmacological targets that can be utilized to minimize it with mechanisms, effects, side effects, and research developmental progress.
Educational summary of published research — not medical advice. License: cc by. Full text is shown only where licensing permits.