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Publications

Journal Article Ppublish 6 citations

PubMed: 41362110 DOI: 10.1002/jcsm.70147

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

J Cachexia Sarcopenia Muscle 16(6):e70147

Authors: Stephan von Haehling, Ryosuke Sato, Henning Langer, Muhammad Shahzeb Khan, Andrew J S Coats, William Evans, Steven Heymsfield, Stefan D Anker

Affiliations

  • Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany.
  • German Center for Cardiovascular Research (DZHK), Partner Site Lower Saxony, Göttingen, Germany.
  • Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Baylor Scott and White Health-The Heart Hospital, Plano, Texas, USA. Baylor Scott and White Research Institute, Dallas, Texas, USA.
  • Heart Research Institute, University of Sydney, Sydney, Australia.
  • Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, California, USA.
  • Division of Geriatrics, Duke University Medical Center, Durham, North Carolina, USA.
  • Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
  • Department of Cardiology (CVK), German Heart Center Charité, Berlin, Germany.
  • German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.

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.

MeSH

Glucagon-Like Peptide 1, Muscles, Pharmaceutical Preparations, Body Composition, Obesity, Patient Reported Outcome Measures, Therapeutics, Sarcopenia