Research reviewed through August 17, 2026. This book prioritizes randomized trials, body-composition substudies, systematic reviews, consensus definitions, and multi-society guidance. A result is described as lean mass unless the study measured skeletal muscle more directly.

Core guidance and definitions

Mozaffarian D, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory. Obesity. 2025. Multi-society clinical advisory; recommendations combine direct and extrapolated evidence. The article reports author disclosures.
Cruz-Jentoft AJ, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing. 2019. Expert consensus from EWGSOP2, not a GLP-1 treatment trial.
Neeland IJ, et al. Changes in lean body mass with glucagon-like peptide-1–based therapies and mitigation strategies. Diabetes, Obesity and Metabolism. 2024. Clinical review of mixed evidence; author conflicts are disclosed in the publication.
US Food and Drug Administration. WEGOVY (semaglutide) prescribing information. Revised February 2026. Current US labeling; pregnancy section 8.1. The separate MASH indication has different risk-benefit language.
US Food and Drug Administration. ZEPBOUND (tirzepatide) prescribing information. Revised 2026. Current US labeling; pregnancy section 8.1.

Body composition during GLP-1–based treatment

Wilding JPH, et al. Impact of semaglutide on body composition in adults with overweight or obesity: exploratory analysis of STEP 1. Journal of the Endocrine Society. 2021. Exploratory DXA analysis of a 140-person randomized-trial subset; STEP 1 was sponsored by Novo Nordisk.
Look M, et al. Body composition changes during weight reduction with tirzepatide in SURMOUNT-1. Diabetes, Obesity and Metabolism. 2025. Post hoc DXA substudy with 160 evaluable participants; SURMOUNT-1 was sponsored by Eli Lilly.
Karakasis P, et al. Effect of GLP-1 receptor agonists and co-agonists on body composition. Metabolism. 2025;164:156113. Systematic review and network meta-analysis of 22 randomized trials; author grant and consulting disclosures appear in the publication.
Laverde LP, et al. Effect of GLP-1 receptor agonists at doses for obesity management on muscle health. International Journal of Obesity. 2026. Systematic review and meta-analysis of seven randomized trials; the authors reported no competing interests.

Protein, exercise, and function

Kokura Y, et al. Enhanced protein intake for maintaining muscle mass, strength, and physical function in adults with overweight or obesity. Clinical Nutrition ESPEN. 2024. Systematic review and meta-analysis of 47 weight-loss studies; not a direct semaglutide or tirzepatide intervention review.
Jensen SBK, et al. Effects of exercise, liraglutide, or both on physical fitness after diet-induced weight loss. 2026. Secondary analysis of a randomized trial; the trial reports public and industry support and author disclosures.
Jensen SBK, et al. Bone health after exercise alone, GLP-1 receptor agonist treatment, or combination treatment. JAMA Network Open. 2024. Randomized secondary analysis; bone is not muscle, and funding and disclosures appear in the article.
LEAN-PREP: resistance exercise and protein during GLP-1 therapy. Registered randomized trial. Ongoing; a registration is not evidence of efficacy, and no results are used in this book.

Research horizon

Pratley RE, et al. Apitegromab for lean mass preservation during tirzepatide-induced weight loss. Nature Medicine. 2026;32:2673–2678. Randomized, double-blind, placebo-controlled phase 2 trial in 102 adults; Scholar Rock sponsored the study, and several authors were employees and equity holders.

Researchers are testing behavioral and pharmacologic approaches intended to improve the quality of weight loss. A 2026 phase 2 trial reported less lean-mass loss when investigational apitegromab was added to tirzepatide, with similar total weight loss. The study was small, enrolled mostly women, used 80% confidence intervals for its primary comparison, and did not show a notable physical-function advantage. Apitegromab is not an established or generally available muscle-preservation treatment for people taking tirzepatide.

The most important unanswered questions include how much DXA or BIA lean-mass change represents contractile skeletal muscle; which patients face the greatest functional risk; which protein calculation is best at different body sizes; what resistance programs are safe, effective, and sustainable; and whether benefits persist across age, sex, frailty, diabetes status, and medication type.