Semaglutide combined with trevogrumab and garetosmab: what the trial evidence shows

Why muscle loss during GLP-1 treatment became the research problem to solve

When people lose substantial body weight (whether through diet, surgery, or a GLP-1 medicine like semaglutide) the reduction is never purely fat. Lean mass, including skeletal muscle, falls too. In the STEP 1 trial, published in the New England Journal of Medicine, participants on semaglutide 2.4 mg lost an average of around 15% of their body weight over 68 weeks. Impressive, but a meaningful share of that came from lean tissue.

Muscle matters beyond appearance. It governs metabolic rate, physical function, and long-term weight maintenance. Losing it during treatment can leave people weaker and more prone to regain. That gap in the GLP-1 story is precisely what the trevogrumab and garetosmab combination was designed to address. By blocking activin A and activin B respectively (two proteins in the myostatin pathway that signal the body to limit muscle growth) the antibodies aim to counteract the lean-mass attrition that otherwise accompanies rapid weight loss.

This isn't a fringe hypothesis. The myostatin pathway is one of the most studied brakes on muscle development in biology, and blocking it has long been a target in conditions like muscle-wasting diseases. Applying that science to obesity pharmacotherapy is a logical next step, even if the clinical evidence is still young.

What the phase 2 trial of this combination actually found

In 2024, Regeneron published phase 2 data from a randomised trial in adults with obesity receiving semaglutide. Participants were split across four groups: semaglutide alone, semaglutide plus trevogrumab, semaglutide plus garetosmab, and semaglutide with both antibodies combined. Body composition (specifically lean mass versus fat mass) was a central endpoint alongside total weight change.

The headline finding: the groups receiving the antibody combination alongside semaglutide lost a similar or greater total amount of weight but retained significantly more lean mass than those on semaglutide alone. In practical terms, a larger proportion of the weight lost came from fat rather than muscle. There were also signals of improvement in measures of physical function. The trial was relatively short and the participant numbers small, phase 2 trials are designed to test signals and guide dose-selection, not to establish the scale of benefit seen in phase 3 programmes.

Safety data at this stage were broadly consistent with what is known about semaglutide's GI-led side-effect profile, detailed on the NHS semaglutide medicines page, with the antibodies adding injection-site reactions as an additional consideration. Longer and larger studies are needed before the benefit-risk picture is clear enough to inform regulatory submissions.

Where this research sits today (and what it means for anyone considering semaglutide

Neither trevogrumab nor garetosmab has been submitted to the MHRA for approval, and neither is available through any UK pharmacy, including nume) the correct spelling: our pharmacy dispenses only MHRA-licensed medicines. This is squarely investigational science. Phase 3 trials are expected to follow, but the timeline from positive phase 2 signals to UK marketing authorisation typically spans several years and requires a successful regulatory review.

For people currently on or considering semaglutide for weight management, the practical takeaway is narrower than the headlines suggest. The best-evidenced way to preserve lean mass during treatment remains resistance exercise and adequate protein intake alongside the medicine, advice any prescriber will offer at consultation. Keeping the pen in the fridge door where you'll see it each morning is one habit; building in a strength session two or three times a week is another that current evidence firmly supports.

The research into muscle-composition outcomes during semaglutide treatment is genuinely exciting for the field. It also illustrates why weight loss pharmacology has moved well beyond simply asking how many kilograms disappear on a scale. Related combination research (such as the work pairing bimagrumab with semaglutide, which targets a different but overlapping pathway) reflects the same scientific momentum. None of it changes what is available and licensed right now.

If you're weighing up what a licensed semaglutide treatment programme could offer you today, our weight loss treatment overview sets out the options, and the FAQs cover the questions our prescribers hear most often. For those curious about how immunity or tolerance can develop over time on semaglutide, there's a dedicated page exploring whether the medicine stops working.

Speak to our prescribers through a free consultation if you'd like to discuss whether Wegovy is right for you, and if you want a broader picture of the treatment before booking, our semaglutide overview page covers everything from how the medicine works to what a typical programme looks like. Clinical suitability is always assessed individually, and for those who have questions about how the medicine might affect other areas of health, our page on semaglutide and erectile dysfunction addresses one topic our prescribers are asked about more than you might expect. The combination research described here won't alter that conversation until regulators have reviewed far more data.