Balancing Weight Loss and Muscle Preservation During GLP-1-Based Therapy for Type 2 Diabetes and Obesity: A Clinical Review

Authors

Elizabeth N. Parker, University of LynchburgFollow

Specialty

Research Medicine

Advisor

Dr. Tom Colletti, DHSc, PA-C, DFAAPA

Abstract

ABSTRACT

This review examines skeletal muscle loss associated with GLP-1RAs and dual GLP-1/GIP-RAs, widely used therapies for T2DM and obesity. While these agents demonstrate robust efficacy in glycemic control and weight loss, evidence indicates that approximately 20% to 30% of the weight reduction may result from loss of lean body mass, with skeletal muscle representing a critical component. This has important implications for metabolic health, physical function, and sustainability of weight management. The review synthesizes clinical trial data to clarify the extent and clinical relevance of muscle loss, addressing misconceptions fueled by media reports that may overstate the risk. Variability in assessment methods, including DEXA and MRI, is discussed to contextualize findings and highlight methodological limitations. Potential mitigation strategies are explored, such as resistance exercise and emerging pharmacologic combinations like GLP-1RAs with amylin analogs, which show promise in promoting fat loss while preserving muscle mass. Despite limitations in current research, such as small sample sizes and inconsistent body composition measures, ongoing studies are expected to refine understanding and support treatment paradigms that emphasize not just weight loss but also optimized body composition and functional health. This review provides evidence-based insights to help clinicians optimize GLP-1–based therapies by balancing the benefits of weight loss with strategies to preserve skeletal muscle and improve long-term outcomes in T2DM and obesity.

Recommended Citation

Parker EN. Balancing Weight Loss and Muscle Preservation During GLP-1-Based Therapy for Type 2 Diabetes and Obesity: A Clinical Review. University of Lynchburg DMSc Doctoral Project Assignment Repository. 2025; 7(3).