A new drug may preserve muscle mass during weight loss, according to early-stage research that raises the prospect of a more complete approach to slimming treatments. The study, published in Nature Medicine, examined whether the monoclonal antibody apitegromab could counteract the loss of lean body tissue – including muscle – that commonly occurs when patients use GLP-1 based injections such as tirzepatide, the active ingredient in Mounjaro and Zepbound.
While these weight-loss drugs have proved highly effective, experts have long warned that not all of the weight lost is fat. Studies suggest that between 25% and 40% of total weight loss on such medications is attributable to a reduction in lean body mass. This matters because lean tissue burns more calories than fat, helps maintain physical strength and is linked to a lower risk of type 2 diabetes. In older adults, muscle loss can also exacerbate age-related sarcopenia, raising concerns about long-term mobility and health.
Apitegromab works by blocking a protein called myostatin, which acts as a natural brake on muscle growth. By inhibiting myostatin, the drug is designed to promote muscle development and strength – a mechanism distinct from GLP-1 agonists, which primarily target appetite and satiety. Originally developed by Scholar Rock for the rare neuromuscular disease spinal muscular atrophy (SMA), apitegromab has shown promise in improving motor function in SMA patients and is currently under regulatory review by the FDA and the European Medicines Agency for that indication. Scholar Rock is now exploring partnerships to develop the drug for obesity and has indicated that it is administered via intravenous infusions.
Trial results
The clinical trial involved 102 participants who were randomly divided into two groups. One group of 51 received apitegromab alongside tirzepatide, while the other 51 received a placebo with tirzepatide. The trial, funded by Scholar Rock, lasted 24 weeks.
Overall weight loss was similar between the two groups. However, those given apitegromab lost on average 1.6kg of lean mass, corresponding to 14.6% of their total weight loss. In contrast, participants who received the placebo lost an average of 3.5kg of lean mass, or 30.2% of total weight loss. This means apitegromab was associated with a 55% greater retention of lean mass relative to the placebo. The number of participants experiencing side-effects was similar between the groups, with most reported as mild.
The researchers noted limitations: the study was small and short in duration, and most participants were women. Further research is needed to assess the drug’s effects across diverse populations, including men and people with pre-existing cardiometabolic conditions.
Expert views and next steps
Professor Alexander Miras, an obesity expert at Ulster University who was not involved in the work, described the findings as “very important”. He noted that while GLP-1 based drugs have been associated with improved “functionality” – making everyday activities easier – they have also been linked to a loss of muscle mass and strength. “This means that [people] may be less able to lift heavy weights, for example, or walk up a hill,” he said. “This new medication may help reduce the effects of GLP-1-based drugs on muscle strength and therefore improve functionality even further compared to someone not on the new medication who is just taking tirzepatide.”
Other experts urged caution. Professor Naveed Sattar, a cardiometabolic medicine specialist at the University of Glasgow, said far larger-scale and longer trials were now needed, not least to check safety. “This is an early-stage trial that suggests novel drugs can help mitigate muscle mass loss with prescribed tirzepatide. However, it’s too early to say whether this actually benefits peoples health or ability to move or function better,” he said.
In the meantime, Sattar emphasised the importance of lifestyle measures. “People prescribed these drugs should be supported to increase their physical activity, as this can help maintain muscle mass in a physiological way. Importantly, activity should also be framed as something enjoyable and sustainable, rather than purely as a medical add‑on,” he added. Experts also recommend adequate protein intake and strength training as complementary strategies.
Other research is exploring similar avenues. A combination of semaglutide and bimagrumab has shown promise in preserving lean mass during weight loss, while a mouse study has suggested that an existing drug, MF-300, might mitigate muscle regeneration issues associated with GLP-1 use. Apitegromab itself remains an investigational drug for weight management and has not yet received regulatory approval for that purpose; its primary development remains for SMA, with decisions from the FDA and EMA anticipated in late 2025 and 2026.