A new class of experimental weight-loss drugs is shifting the focus of obesity treatment from simply dropping pounds to preserving muscle mass. Pharmaceutical companies and academic researchers are advancing treatments designed to burn fat and maintain lean tissue, addressing a major drawback of current blockbuster therapies like Ozempic.
The Muscle Loss Problem in Modern Weight Loss Drugs
Current medications such as Ozempic, Mounjaro, and Zepbound belong to a class of drugs known as GLP-1 receptor agonists. According to industry reporting by Business Insider, these drugs primarily work by dampening appetite and slowing digestion, which causes patients to eat less and lose weight rapidly. However, biology dictates that faster weight loss often triggers the body to burn both fat and muscle for energy.
According to Lloyd Klickstein, founder of the biotech startup Versanis, the medical field is shifting its perspective on what constitutes successful treatment. “We had blinders on with respect to what muscle does,” Klickstein told Business Insider, noting that the industry previously focused on muscle’s power function rather than its role as a metabolism regulator. Physicians note that significant lean mass loss can lead to frailty and weaker bones, making some doctors hesitant to prescribe GLP-1 medications to vulnerable patients.
Emerging Pipeline Drugs and Repurposed Compounds
To combat muscle wasting, several pharmaceutical companies are developing new drug candidates or repurposing older, failed molecules:
- Bimagrumab: Originally tested by Novartis as a treatment for age-related muscle loss called sarcopenia, this molecule was acquired by Eli Lilly through its $1.9 billion purchase of Versanis in 2023. According to Business Insider, the drug promotes fat loss while actively preserving muscle.
- SPX-001: Designed to preserve lean mass while patients take a GLP-1 medication, this candidate was acquired by AstraZeneca for approximately $300 million in 2025, as reported by Business Insider.
- CagriSema: Developed by Novo Nordisk, this next-generation GLP-1 aims to help patients lose more fat and retain more muscle compared to Ozempic.
- ATX-304: Developed by New York-based Cambrian Biotech, this experimental compound aims to mimic the metabolic effects of exercise. According to Cambrian CEO James Peyer in comments reported by Business Insider, taking the pill is metabolically comparable to running five to ten kilometers daily without the associated physical exertion. Unlike GLP-1 drugs, ATX-304 is designed to increase metabolic rate and make fat and muscle burn more energy rather than suppressing appetite.
Alternative Approaches Targeting Appetite and Calorie Burning
Researchers are also exploring novel targets beyond the GLP-1 pathway. A study published in the journal Nature examined a drug candidate targeting the neurokinin 2 receptor, or NK2R. According to BBC Science Focus, the treatment aims to curb appetite and boost calorie burning simultaneously.
Dr. Zach Gerhart-Hines, an Associate Professor at the University of Copenhagen and co-author of the NK2R study, told BBC Science Focus that the compound drove weight loss while sparing lean mass compared to semaglutide. Furthermore, Gerhart-Hines noted that the drug did not trigger the significant aversive nauseating responses often associated with high doses of semaglutide.
Despite the laboratory findings in overweight mice, some independent experts remain cautious. Dr. Adam Collins, an Associate Professor at the University of Surrey who was not involved in the research, told BBC Science Focus that the study is currently hypothetical based on animals and expressed skepticism regarding its application and rationale for humans.
Researchers working on the NK2R pathway aim to begin human clinical trials within the next two years, while companies advancing exercise-mimicking pills and muscle-preserving biologics continue early-stage human evaluations.
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