Weight loss without muscle loss? The next generation of drugs is testing the idea

• Weight loss always comes with some muscle loss.
• A growing number of drugmakers are trying to stop that, with molecules that preserve lean mass.
• Some drugs mimic exercise, others stop muscle breakdown.

Nearly every pharmaceutical company you can name is chasing this tantalizing idea: hang on to your muscles while you lose weight.

It's a goal that seems to defy the laws of biology — our bodies are wired to lose both fat and at least some muscle during weight loss. Faster weight loss often means more muscle loss, as the body scrambles to quickly find extra energy to burn. This has been one of the glaring problems with GLP-1 drugs like Ozempic, Mounjaro, and Zepbound: some patients lose a lot of muscle, becoming frail.

A bounty of emerging drug candidates promise to fix this issue. There's bimagrumab, a molecule that promotes fat loss while preserving muscle (made by startup Versanis and acquired by Eli Lilly for $1.9 billion in 2023). SPX-001 is designed to preserve lean mass while taking a GLP-1 (snapped up by AstraZeneca for about $300 million in 2025). Novo Nordisk hopes its next-generation GLP-1, CagriSema, will help patients lose more fat and retain more muscle than their previous blockbuster, Ozempic, did.

On Friday, another startup upped the ante. Cambrian Biotech, a late-stage VC-backed pharmaceutical company based in New York, released early results of the first human study of a drug that mimics exercise. Taking it, the company's CEO said, is like running 5-10k every day, metabolically speaking, but without the sweaty mess. Unlike GLP-1 drugs, which dampen appetite and slow digestion, this drug is designed to simply incinerate more calories every day. The goal, which still needs to be evaluated in larger clinical trials, is to turn up the dial on how the body uses stored fuel.

"We want a different tool that increases your metabolic rate, makes your fat metabolically active, makes your muscles burn more energy," Cambrian CEO James Peyer told Business Insider.

Doctors are relieved to see these drug candidates advancing. GLP-1 drugs are game-changers for metabolic disease, but some physicians hesitate to prescribe them when the inevitable muscle loss that comes with weight loss can be dangerous, leading to frailty and weaker bones. Plus, when you're eating less on a GLP-1, muscle-building — which requires getting enough protein and calories to fuel muscle growth — is an even bigger challenge.

The rise of muscle-preserving drug candidates is also being bolstered by a growing recognition that muscles aren't just about strength; they're metabolism regulators. Keep the muscles strong, and you can help improve all kinds of metabolic disease processes in the body, from diabetes to liver failure, without worrying so much about exactly how much protein you're eating, or how often you're lifting heavy.

"I think everybody is now seeing that maybe we have addressed the magnitude of the weight loss problem," Versanis founder and serial biotech entrepreneur Lloyd Klickstein told Business Insider. "Now, we need to reconfigure our thinking towards addressing the quality of the weight loss."

Yesterday's failed drugs are becoming today's hottest biotech jewels

A lot of the excitement we're seeing in this field is being driven by pharmaceutical companies taking old, failed drugs back off the shelf.

Bimagrumab, the molecule that Eli Lilly acquired from Versanis, is a perfect example of this: it is a failed muscle-wasting drug that was initially tested in older people with age-related muscle loss, called sarcopenia. In a series of large-scale clinical trials conducted by Novartis from 2014 to 2018, it just didn't work.

"We had blinders on with respect to what muscle does," Klickstein said. "Everybody was still thinking about the power function of muscle, and less about the metabolic function of muscle."

Then, investors revisited the drug with a new goal: simply recycling and maintaining muscle, rather than creating more. Suddenly, it looked like a game changer. Eli Lilly's latest trial of bimagrumab, which included over 500 people with obesity, showed that those who added the drug to an Ozempic prescription lost an average of more than 90% of their body fat.

It's worth pointing out how remarkable that is. For as long as scientists have been measuring weight loss, they've seen people typically lose roughly 65-75% fat and about 25-35% lean mass.

In addition to repurposed drugs like bimagrumab, pharmaceutical makers are pursuing new combinations of existing tools. Novo Nordisk's CagriSema, a combination of Ozempic and a new diabetes drug called cagrilintide, netted 67% fat loss in patients with obesity. It may be a little more powerful than Ozempic, but it doesn't appear to break through the tried-and-true weight-loss equation.

Then there are the biotech moonshots: new drugs that promise to completely reimagine how human metabolism works — if they prove successful.

In a small, initial safety trial of 23 adults that Cambrian presented at the American Diabetes Association conference earlier this month, prediabetic patients with obesity taking their once-daily pill increased their resting metabolic rate and lost about 5% of their visceral fat, the dangerous, inflammatory kind that hugs internal organs and is linked to more chronic disease. A midsize trial that will begin to deliver a clear picture of what this drug — ATX-304 — can really do is slated to read out at the end of 2027.

From bodybuilders to older adults, there's a gigantic potential market for these drugs

The concept of body recomposition — losing fat and gaining muscle in tandem — is alluring across demographics.

Think of bodybuilders, post-menopausal women, and aging grandparents who can't work out like they used to; there would be numerous potential use cases for this kind of drug outside of obesity medicine.

But we don't yet know whether any of these drugs will ever clear the required hurdles with the US Food and Drug Administration, or whether their intended use cases will spark interest from key payers like Medicare and private insurers.

In short, whether doctors will ever pull out their pen and pad and write a prescription for this kind of muscle-retaining, metabolism-boosting therapy is still a subject of heated debate in the medical world.

"No one is going to write a prescription for body composition changes," Daniel Drucker, an endocrinologist at the University of Toronto, told Business Insider.

Drucker was instrumental in the discovery of the role of the GLP-1 hormone in diabetes, paving the way to the formulation of Ozempic.

He'd like to see drugs come to market targeting sarcopenia directly and successfully, for the "hundreds of millions of older people who are frail and fragile and could really benefit." But he voiced skepticism about the rapidly growing field of muscle-preserving drug candidates, which haven't yet shown they can deliver clinically meaningful results, like preventing more falls, improving strength, or increasing walking speed in older patients.

It's possible that drugmakers will start incorporating some of these therapies into combination drugs. One day, things like Ozempic or Zepbound could be combined with something like bimagrumab or Cambrian's exercise pill, in a single prescription.

"You give me all the benefits of these GLP-1 medicines, plus you tag on something that builds lean mass and ideally muscle strength?" Drucker said. "I see that as a winning strategy."

He thinks about his 98-year-old mother, and the huge value add a drug that preserves muscle could be for her and her friends. "Fewer falls, fewer fractures, fewer emergency room visits," he said. But he knows old people like his mom aren't the only ones who'd be excited about taking this kind of muscle-retaining substance.

"You get your drug approved, and then everybody in the gym is going to buy it," he said.