Countless drug developers are pursuing an appealing concept: retain muscle tissue even as body weight decreases.

This objective appears to challenge natural processes, since human physiology typically sheds both fat and some muscle when slimming down. Quicker reductions in weight frequently result in greater muscle decline, as the system rapidly seeks additional fuel sources. One notable drawback of GLP-1 medications such as Ozempic, Mounjaro, and Zepbound involves substantial muscle reduction in certain users, which can lead to weakness.

Numerous new candidates aim to resolve this challenge. Bimagrumab encourages fat decrease while safeguarding muscle and was developed by Versanis before its purchase by Eli Lilly for 1.9 billion dollars in 2023. SPX-001 aims to maintain lean tissue during GLP-1 use and was acquired by AstraZeneca for roughly 300 million dollars in 2025. Novo Nordisk anticipates that its advanced GLP-1 option, CagriSema, will enable greater fat loss and better muscle preservation compared to the earlier success of Ozempic.

Recently, a fresh startup raised the stakes further. Cambrian Biotech, a New York-based firm in later-stage venture funding, shared initial findings from the inaugural human trial of an exercise-mimicking compound. According to the chief executive, its effects equate to daily runs of 5 to 10 kilometers in metabolic terms, yet without physical exertion. In contrast to GLP-1 agents that curb hunger and delay digestion, this option focuses on elevating daily calorie burn. The objective, pending confirmation in broader studies, involves adjusting how the body utilizes stored energy reserves.

"Our aim is an alternative approach that elevates metabolic activity, activates fat for energy use, and prompts muscles to expend additional fuel," Cambrian CEO James Peyer explained to Business Insider.

Medical professionals welcome progress on these candidates. While GLP-1 treatments transform care for metabolic conditions, some clinicians remain cautious about prescribing them due to muscle loss risks that may cause frailty or reduced bone density. Moreover, reduced intake on GLP-1 regimens makes muscle development, which demands sufficient protein and calories, more difficult to achieve.

Interest in muscle-preserving options also stems from greater awareness that muscle serves as a key regulator of metabolism. Sustaining muscle strength can positively influence various metabolic issues, including diabetes and liver conditions, while reducing concerns over precise protein intake or resistance training frequency.

"Many now recognize that the scale of weight reduction has been tackled," Versanis founder Lloyd Klickstein noted to Business Insider. "Attention must now shift toward improving the nature of that reduction."

Prior unsuccessful compounds emerge as current biotech highlights

Much of the current enthusiasm arises from companies reviving earlier unsuccessful compounds for fresh applications.

Bimagrumab exemplifies this trend: originally developed by Novartis as a treatment for age-related muscle decline known as sarcopenia, it underwent extensive trials between 2014 and 2018 without success. "Our perspective on muscle function was limited," Klickstein observed. "Focus remained on physical power rather than metabolic roles."

Reevaluating the compound with an emphasis on muscle maintenance instead of growth transformed its potential. Eli Lilly's recent study involving over 500 individuals with obesity found that combining the drug with Ozempic led to more than 90 percent average fat loss.

This outcome stands out, as typical weight reduction historically involves 65 to 75 percent fat loss and 25 to 35 percent lean mass reduction.

Beyond repurposed agents like bimagrumab, developers explore pairings of current options. Novo Nordisk's CagriSema, blending Ozempic with cagrilintide, achieved 67 percent fat loss in obese patients. While potentially stronger than Ozempic alone, it aligns closely with established weight-loss patterns.

Additional efforts include innovative compounds that could redefine metabolic function, assuming they succeed in trials.

In an early safety study of 23 adults presented by Cambrian at the American Diabetes Association meeting this month, prediabetic obese participants using the daily tablet showed elevated resting metabolic rates and about 5 percent reduction in visceral fat, a harmful type linked to chronic illness. A larger upcoming trial for ATX-304 is expected to yield clearer data by late 2027.

Broad appeal spans from fitness enthusiasts to seniors, signaling vast market potential

The idea of simultaneous fat loss and muscle gain attracts diverse groups.

Applications could include bodybuilders, women after menopause, and older adults limited in exercise capacity, extending well beyond obesity treatment.

Success depends on navigating FDA requirements and securing coverage from insurers such as Medicare or private plans.

Ultimately, whether physicians will routinely prescribe such muscle-retaining, metabolism-enhancing therapies remains under discussion.

"Prescriptions will not target body composition alone," stated Daniel Drucker, an endocrinologist at the University of Toronto, in comments to Business Insider.

Drucker contributed to understanding GLP-1's role in diabetes, which supported Ozempic development.

He advocates for direct sarcopenia treatments benefiting millions of frail older adults. Yet he expressed doubts about muscle-preserving candidates, noting insufficient evidence of meaningful outcomes like fewer falls, enhanced strength, or better mobility in seniors.

Combination therapies may emerge, pairing agents like Ozempic or Zepbound with options such as bimagrumab or Cambrian's compound.

"All GLP-1 advantages plus added lean mass and strength gains would represent a strong approach," Drucker suggested.

Considering his 98-year-old mother, he highlighted benefits like reduced falls, fractures, and hospital visits for elderly patients. Still, he noted appeal extends to others as well.

"Approval would likely draw interest from gym-goers too," he added.