Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions

Authors

• Stephan von Haeling, University of Göttingen Medical Center, Göttingen, Germany
• Ryosuke Sato, University of Göttingen Medical Center, Göttingen, Germany
• Henning Langer, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
• Muhammad Shahzeb Khan, Baylor Scott and White Health-The Heart Hospital, Plano, TX
• Andrew J S Coats, Heart Research Institute, University of Sydney, Sydney, Australia
• William Evans, University of California Berkeley, Berkeley, CA
• Steven B. Heymsfield, Pennington Biomedical Research Center, Baton Rouge, LA
• Stefan D. Anker, German Heart Center Charité, Berlin, Germany

Document Type

Article

Publication Date

12-8-2025

Publication Title

Journal of Cachexia, Sarcopenia and Muscle

Abstract

The Society on Cachexia and Wasting Disorders (SCWD) convened a Regulatory and Trial Update Workshop in Washington, D.C., in December 2024, assembling experts from academic institutions, the pharmaceutical industry and the US Food and Drug Administration (FDA) for focused discussions. This article summarizes the latter half of the meeting, which primarily focused on novel anti-obesity therapies based on incretin pathway alteration. Discussions highlighted the impact of glucagon-like peptide-1 (GLP-1) receptor agonists or GLP-1/glucose-dependent insulinotropic polypeptide (i.e., GLP-1/GIP) agonists on body composition and muscle health; the challenges of distinguishing 'true' skeletal muscle from fat-free tissue; the impact of treatment discontinuation and weight regain; advances in imaging and quantitative assessment of lean body mass; as well as insights from emerging muscle-preserving therapies (e.g., bimagrumab, pemvidutide and enobosarm). There are significant challenges in defining meaningful structural, functional and patient-reported endpoints for the use of muscle-'protective' drug therapies in the context of weight loss therapies. These also involve significant regulatory considerations for future drug development and approval pathways, for instance related to the very large number of individuals that may be considered for these therapeutic approaches as well as from the potential long (or life-long) duration of therapy considered with these drugs. Together, these discussions highlight the growing importance of integrating body composition and functional assessments in future clinical trials.

First Page

1

Last Page

15

DOI

10.1002/jcsm.70147

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

von Haeling, Stephan; Sato, Ryosuke; Langer, Henning; Khan, Muhammad Shahzeb; Coats, Andrew J S; Evans, William; Heymsfield, Steven B.; and Anker, Stefan D., "Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions" (2025). LSU-LCMC Cancer Center Faculty Publications. 240.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/240
10.1002/jcsm.70147