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Obesity has escalated into a global epidemic, with over 1 billion individuals affected worldwide, including nearly 880 million adults and 159 million children and adolescents aged 5–19 years (World Obesity Federation). This surge in obesity rates is closely linked to a heightened risk of chronic diseases such as type 2 diabetes, cardiovascular diseases, and certain cancers.
In response to this crisis, glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a groundbreaking class of medications for weight management. Drugs like semaglutide (marketed as Ozempic and Wegovy) mimic the GLP-1 hormone, enhancing insulin secretion, suppressing appetite, and slowing gastric emptying, thereby promoting weight loss.
Benefits of GLP1 drugs (Source: Everyday Health)
Unintended Consequences: Muscle Loss
While GLP-1 therapies have demonstrated remarkable efficacy in weight reduction, recent clinical trials have highlighted a concerning side effect: significant loss of lean muscle mass. A 2024 study published in The Lancet reported that approximately 25–39% of the weight lost through GLP-1 treatment is lean mass, not fat (Prado et al. 2024). This muscle loss can impair metabolic health, reduce physical strength, and accelerate aging processes.
Weight Loss Drug Comparison: Efficacy, Muscle Loss, and Market Stage
Towards a Dual-Action Approach: Fat Loss and Muscle Preservation
Recognizing the need for a more balanced approach to weight management, pharmaceutical innovators are now focusing on therapies that not only promote fat loss but also preserve or enhance muscle mass (Rodgers and Christopher 2022). One promising solution is to pair GLP-1 therapies with agents that block negative muscle regulators like activin receptor type II (ActRII) and ligands such as GDF8 (myostatin) and activin A. A 2025 Nature Communications study (Mastaitis et al. 2025) showed that combining semaglutide with GDF8/activin A blockers preserved lean mass and enhanced fat loss in preclinical models. Regeneron’s Phase 2 COURAGE trial echoed these results in humans: combination therapy significantly reduced fat while preserving up to 81% of lean mass loss compared to semaglutide alone.
At the American Diabetes Association (ADA) 2025 conference:
Eli Lilly presented bimagrumab plus semaglutide for improved muscle retention.
Laekna showcased LAE102 (ActRIIA antibody) for muscle regeneration and fat loss.
Ascletis reported enhanced fat loss with ASC47 in semaglutide combo studies.
Together, these innovations signal a paradigm shift—moving beyond weight loss to healthier, functionally optimized bodies.
Supporting Research and Development: The Role of Biocytogen
To facilitate the development of these next-generation therapies, Biocytogen offers a comprehensive portfolio of obesity-related mouse models. These include monogenic, diet-induced, and single- or multi-target humanized models targeting appetite regulation, incretin signaling, and metabolic pathways, providing invaluable tools for advanced preclinical research and drug discovery.
Case Study 1: GLP1R Agonists and ActRII Ab on Fat and Lean Mass |
Efficacy of GLP1R agonists and ActRII antibody on fat mass and lean mass in B-DIO mice. (A-B) Body weight change after treatment. (C) Fat mass and lean mass change analyzed by Micro-CT scan. (D) Micro-CT images of total adipose tissue and lean tissue in mice after treatment. Mean ± SEM. Semaglutide (GLP-1R agonist) reduces fat; Bimagrumab (ActRII Antibody) promotes muscle growth; Tirzepatide is a dual agonist of GLP-1 and GIP receptors. |
Case Study 2: Semaglutide in HFD-Induced Humanized GLP1R Mice |
Efficacy study of semaglutide in HFD-induced B-hGLP1R mice. (A) Body weight change after HFD induction. (B-C) Body weight change after semaglutide treatment. (D-E) Effect of semaglutide on food intake. Mean ± SEM. |
Case Study 3: GIPR Antibody in HFD-Induced Humanized GIPR Mice |
Efficacy study of human GIPR-antibody in HFD-induced B-hGIPR mice. B-hGIPR mice were fed with a high-fat diet for 12 weeks to induce mice obesity. (A) Body weight change after HFD induction. (B-C) Body weight change and food intake (day21) after hGIPR-antibody Amgen (2G10) analog (in house), Semaglutide, and combination treatment. (D) Blood biochemical analysis after treatment. Mean ± SEM. |
Featured Mouse Models for Obesity & Diabetes at Biocytogen |
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Literature Reference:
Prado, Carla M., et al. "Muscle matters: the effects of medically induced weight loss on skeletal muscle." The Lancet Diabetes & Endocrinology 12.11 (2024): 785-787.
Rodgers, Buel D., and Christopher W. Ward. "Myostatin/activin receptor ligands in muscle and the development status of attenuating drugs." Endocrine Reviews 43.2 (2022): 329-365.
Mastaitis, Jason W., et al. "GDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates." Nature Communications 16.1 (2025): 1-8.
Website Reference:
“Prevalence of Obesity.” World Obesity
“Health Risks of Being Overweight.” NIDDK, U.S. Department of Health and Human Services
“Obesity: Health Consequences of Being Overweight.” World Health Organization
“Obesity and Cancer Fact Sheet.” National Cancer Institute, U.S. Department of Health and Human Services
“GLP-1 Drugs for Obesity and Weight Loss.” Everyday Health
“Interim Results from Ongoing Phase 2 COURAGE Trial Confirm Potential of PD-1 Inhibitor Combination in Obese Patients with Solid Tumors.” Regeneron Newsroom, 4 Jan. 2024
