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The co-founder of Regeneron has warned that blockbuster weight-loss drugs could cause “more harm than good” unless the rapid muscle loss associated with the treatments is solved, as the US biotech pushes ahead with trials of muscle-preserving medicines.
Clinical studies suggest that patients treated with the new class of weight- loss drugs, known as GLP-1s, lose muscle at far faster rates than people losing weight from diet or exercise, exposing them to health problems, said George Yancopoulos, who also serves as Regeneron’s chief scientific officer.
For the two in every five patients who discontinue the treatments within a year, according to a 2024 JAMA study, this means that they are likely to rebound to their original weight with less muscle and a higher body fat percentage, “adding insult to injury”, said Yancopoulos.
“I do think that the GLPs should be viewed with a lot of concern in terms of the way they’re actually being used in the real world,” said Yancopoulos. “They could be leading to successive changes in body composition that could be creating more harm than good in the long term.”
Regeneron is among a growing list of drugmakers researching experimental drugs to preserve lean muscle mass in combination with GLP-1 drugs as a route into a potentially $130bn-a-year market that is dominated by Ozempic and Wegovy maker Novo Nordisk and Eli Lilly, the company behind Mounjaro and Zepbound.
Regeneron, a $111bn biotech that specialises in antibody treatments, is testing a drug called trevogrumab, which blocks the hormone myostatin, which limits muscle growth, in combination with Wegovy in mid-stage trials. There are 11 myostatin drugs in biotech pipelines, of which seven are being investigated for obesity, according to industry tracker Citeline.
Last year, Eli Lilly bought Boston-based biotech Versanis in a deal worth $1.9bn to get its hands on its muscle-preserving treatment to complement its weight-loss drugs. BioAge, a biotech with a muscle-regeneration drug that is partnered with Eli Lilly, listed last month and its share price is up 21 per cent.
Clinical data shows that 25 per cent of weight loss from Eli Lilly’s shot resulted from a reduction in lean body mass, including muscle, while 40 per cent of Novo Nordisk’s jab was due to a drop in lean body mass.
The US Food and Drug Administration advises that the drugs be used in combination with diet and exercise. Novo Nordisk said clinical data “[does] not indicate an association of greater lean body mass loss over fat mass loss with semaglutide treatment”. Eli Lilly did not immediately respond to a request for comment.
The first clinical data from Regeneron’s phase-two trial of trevogrumab is expected halfway through next year. Regeneron is also considering whether to advance a monthly GLP-1 injection to clinical trials, which it has tested in mice. Despite his concerns about the drug, Yancopoulos said Regeneron was “thinking about becoming players in the GLPs”.
“I’m not sure that the GLPs are really the true final answer here, because they could have significant long-term problems,” he added.
“We all want to have 10 more pounds of muscle, 10 less fat, but we could eat whatever we want — that’s the ideal world,” said Yancopoulos.
“We don’t all want to be nauseous and sick and losing muscle. I do think that . . . an ideal future is one where we achieve a better, healthier way of fighting back against metabolic disease.”
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