Keeping Muscle While Losing Fat Is Next Goal for Obesity Drugs

(Bloomberg) -- The new blockbuster weight-loss shots can help patients trim more pounds than any medicines have before. Now drugmakers are rushing to solve another problem — making sure people keep their muscle even as they shed fat.

The race for potential treatments is picking up pace. Regeneron Pharmaceuticals Inc. released data recently showing that its antibody cocktail boosted muscle in a small group of volunteers. Eli Lilly & Co. agreed to shell out as much as $2 billion last year for a startup with an experimental drug that aims to decrease fat while maintaining muscle.

Some doctors are skeptical, saying that for many obese patients shedding pounds is of paramount importance, even if they lose muscle alongside fat. Yet preserving muscle is an alluring goal for drugmakers that missed the first generation of obesity treatments and are seeking a foothold in the fast-growing and lucrative field.

For now, Novo Nordisk A/S’s Wegovy and Eli Lilly’s Zepbound are the leading therapies in a weight-loss market that could grow to $100 billion by 2030, according to Goldman Sachs estimates. But both companies are also studying treatments to help patients retain muscle while slimming down.

“We can make people lose weight — now it’s the next step,” said Jennifer Linge, a lead scientist at AMRA Medical AB, a Swedish company that uses body scans to study muscle composition. “The muscle piece will be an important one for the next phase.”

The Weight-Loss Drug Frenzy Is Outrunning The Company Novo Nordisk A/S Behind It

Like obesity, sarcopenia — the loss of skeletal muscle mass and function — was long an ignored disorder, Linge said. It’s usually linked with aging, though chronic diseases such as cancer, HIV and diabetes can also cause the condition.

When people drop weight very quickly, whether via obesity drugs or bariatric surgery, they may face a higher risk of an unhealthy loss of muscle. And if they stop using the drugs and regain weight, they risk adding back a higher proportion of fat, an effect that can weaken the body over time.

The phenomenon is rooted in the body’s ability to raid its own muscles to survive periods of starvation, said George Yancopoulos, chief scientific officer of Regeneron. Severe caloric restriction helps spur the production of myostatin, a protein that impedes the growth of muscle.

Schwarzenegger Mice

In the 1990s, scientists figured out how to knock out the myostatin-creating gene in mice; Yancopoulos called the resulting rodents “little Arnold Schwarzeneggers.”

Although companies have long tried to target myostatin for muscle-wasting disorders, proving it can benefit patients has been a challenge, Yancopoulos said in an interview early this year. But patients losing muscle mass with weight-loss drugs could be a “public health disaster,” he said, one that muscle retention drugs might alleviate.

Regeneron is recruiting hundreds of volunteers to test two different, potentially muscle-boosting antibodies — given together, in some cases, with Novo’s Wegovy. The US biotech is currently testing the drugs on healthy volunteers; by mid-year, it anticipates being able to recruit the first obese patients.

Muscling into the Wegovy hype | Drugmakers are testing ways to help patients lose weight while preserving muscle

In a small study, post-menopausal women who weren’t obese saw their thigh muscles increase in size after taking the experimental drug cocktail, Regeneron said at the European Congress on Obesity in Venice on May 12.

Side effects are a potential concern: Regeneron only recruited post-menopausal women into the first part of the small trial because of a potential for embryo toxicity and reproductive toxicity in men, said trial leader Dinko Gonzalez Trotter, executive director of imaging at Regeneron. The continuing studies will also recruit men and will help make the drugs’ safety profile clear, Regeneron said in an e-mailed statement.

Weight-Loss Drug Zepbound As Patients Face Shortages

To move more quickly, some companies are turning to medicines originally developed for other disorders. Swiss drugmaker Roche Holding AG has said it sees potential to combine an experimental muscular dystrophy drug with a weight-loss compound it acquired in the $3.1 billion Carmot Therapeutics deal.

Eli Lilly is testing a similar hypothesis: The company plans to study its weight-loss drug Zepbound in combination with a treatment that has shown promise preventing muscle atrophy in older adults.

Separately, Lilly is already testing a drug called bimagrumab — acquired last year through its purchase of startup Versanis Bio — to see if it spurs weight loss while preserving muscle.

“Our hope is to see increased ratio of lean to fat mass,” Chief Scientific Officer Dan Skovronsky told investors in April.

Novo is doing its own early work on compounds that could preserve muscle, development chief Martin Holst Lange said this week. Yet Novo has also pushed back against the idea that the muscle loss seen with Wegovy is unhealthy. About 35% of the weight lost on the drug may be lean body mass, Lange said, a proportion he characterized as “normal.”

Read more on muscle loss and anti-obesity drugs

There’s already one proven way to keep more muscle while losing weight: exercise. In a Danish study of Novo’s older GLP-1 drug Saxenda, patients who exercised lost twice as much body fat as those who took Saxenda alone. People who took the drug without working out didn’t necessarily lose less weight, but they were more likely to lose muscle as well as fat.

Muscle Mass

Building muscle can also help prevent patients from regaining weight as quickly if they stop using the drugs, said Signe Torekov, the University of Copenhagen professor who led the study, which was backed by the Novo Nordisk Foundation. That’s because more muscle mass is linked to a higher metabolic rate.

Other doctors note that while muscle mass may be important, how well patients can use their muscles in everyday life is key.

“If you’re 175 kilos (or 386 pounds) and you need medication, you’re worried about muscle mass loss, but your primary thing is that you’re worried about being alive,” said Sean Wharton, medical director of the Wharton Medical Clinic outside Toronto, who helped lead a study of a next-generation obesity pill from Eli Lilly.

“Can’t walk up a flight of stairs? I have a feeling that person’s going to be able to walk up that flight of stairs a lot better 50 kilos lighter, even with the muscle mass that is lost,” he said.

Most Read from Bloomberg

©2024 Bloomberg L.P.