Cigrovski Berkovic M, Ruzic L, Cigrovski V, Strollo F. Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs. World J Diabetes 2025; 16(9): 109123 [DOI: 10.4239/wjd.v16.i9.109123]
Corresponding Author of This Article
Maja Cigrovski Berkovic, MD, PhD, Associate Professor, Department of Sport and Exercise Medicine, University of Zagreb Faculty of Kinesiology, Horvacanski Zavoj 15, Zagreb 10000, Croatia. maja.cigrovskiberkovic@gmail.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Sep 15, 2025; 16(9): 109123 Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.109123
Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs
Maja Cigrovski Berkovic, Lana Ruzic, Vjekoslav Cigrovski, Felice Strollo
Maja Cigrovski Berkovic, Lana Ruzic, Department of Sport and Exercise Medicine, University of Zagreb Faculty of Kinesiology, Zagreb 10000, Croatia
Vjekoslav Cigrovski, Department of Sport, University of Zagreb Faculty of Kinesiology, Zagreb 10000, Croatia
Felice Strollo, Department of Endocrinology and Metabolism, IRCCS San Raffaele Pisana, Rome 00163, Italy
Author contributions: Cigrovski Berkovic M contributed to manuscript conceptualization, drafting, and writing; Cigrovski Berkovic M, Ruzic L, Cigrovski V, and Strollo F contributed to data collection, analysis, and writing of the final version; and all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maja Cigrovski Berkovic, MD, PhD, Associate Professor, Department of Sport and Exercise Medicine, University of Zagreb Faculty of Kinesiology, Horvacanski Zavoj 15, Zagreb 10000, Croatia. maja.cigrovskiberkovic@gmail.com
Received: April 30, 2025 Revised: May 23, 2025 Accepted: August 20, 2025 Published online: September 15, 2025 Processing time: 135 Days and 1.2 Hours
Abstract
Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications, with cardiovascular disease being a leading cause of mortality. Losing 5%-10% of body weight is considered clinically significant for improving health. This weight loss can be achieved through pharmacotherapy, including glucagon-like peptide 1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insulinotropic peptide dual receptor agonists, and GLP-1/glucose-dependent insulinotropic peptide/glucagon triple receptor agonists (such as semaglutide, tirzepatide, and retatrutide, respectively). While much of the weight loss comes from fat mass, these treatments also result in the loss of lean mass, including muscle. This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia. Therefore, the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass, ideally promoting muscle gain. Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction, which may play a crucial role in preserving both muscle mass and function. We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes. Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.
Core Tip: Weight loss medications can lead to a reduction in both fat and muscle mass. Losing muscle can make it more difficult to maintain weight in the long term, and can increase the risk of sarcopenia, as well as the likelihood of regaining weight due to unfavorable changes in body composition. Therefore, it is essential for new medications to focus on preserving muscle mass or even promoting the growth of lean mass as part of weight maintenance programs. Additionally, research is being conducted on the release of myokines during muscle contraction and their roles in autocrine, paracrine, and endocrine functions related to muscle preservation.
