Bimagrumab and Semaglutide: Fat Loss That Spares Muscle

The defining question in obesity medicine is shifting from how much weight a drug removes to what kind of tissue it removes. Bimagrumab sits at the center of that shift. It is not a GLP-1 drug at all — it is a monoclonal antibody that blocks the activin type II receptors on muscle — but its most consequential data come from pairing it with semaglutide. In the phase 2 BELIEVE trial, that combination produced some of the largest weight reductions reported for an injectable regimen while protecting, and even adding to, lean muscle mass. For a field increasingly worried that GLP-1 medications strip away muscle along with fat, bimagrumab represents a genuinely different mechanism aimed squarely at the problem.

Why muscle loss became the central problem of GLP-1 weight loss

When someone loses weight through any method — diet, surgery, or medication — a fraction of that loss comes from lean tissue rather than fat. With the current generation of GLP-1 receptor agonists, that fraction has turned out to be substantial. Pooled analyses estimate that lean body mass accounts for roughly 25% to 39% of total weight lost over 36 to 72 weeks of treatment.

Evidence: "Reductions in fat-free mass with GLP-1-based therapies typically represent 25–39% of total weight lost, a proportion comparable to that seen with caloric restriction, underscoring the need for mitigation strategies such as increased protein intake and resistance exercise." — Neeland IJ, et al. Diabetes, Obesity and Metabolism. 2024. DOI

The semaglutide trials illustrate the pattern. In STEP 1, semaglutide 2.4 mg produced a mean 14.9% body-weight reduction at 68 weeks, and an exploratory body-composition analysis found that total lean body mass fell by roughly 9.7% from baseline even as fat mass fell further and the ratio of lean to fat tissue improved.

Evidence: "The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo." — Wilding JPH, et al. New England Journal of Medicine. 2021. DOI

Whether that lean-mass loss matters clinically is the subject of active debate. Much of the lost lean tissue is metabolically inert water and connective tissue rather than contractile muscle fiber, and in younger patients the loss is often proportional to the smaller body they now carry. But in older adults, in people with low baseline muscle, and in anyone losing weight very rapidly, shedding functional muscle can compromise strength, metabolic rate, and long-term weight maintenance. That concern is what reframed the goal from quantity to quality — and what created an opening for a muscle-targeted drug. We cover the underlying biology and practical countermeasures in our guide to preserving lean mass on GLP-1 medications.

Evidence: "Skeletal muscle is the largest reservoir of protein and a key determinant of metabolic health and physical function; the rapid, profound weight loss now achievable with pharmacotherapy makes the preservation of muscle an explicit therapeutic target rather than an afterthought." — Prado CM, et al. The Lancet Diabetes & Endocrinology. 2024. DOI

What bimagrumab is and how it works

Bimagrumab is a fully human monoclonal antibody that binds and blocks the activin type II receptors (ActRII) found mainly on skeletal muscle. Those receptors normally receive signals — from myostatin and activins — that restrain muscle growth. By blocking them, bimagrumab releases that brake, and muscle fibers enlarge. The drug's second, less obvious effect is on adipose tissue: in trials it consistently reduces fat mass, including the visceral fat packed around the abdominal organs that drives metabolic disease.

This makes bimagrumab mechanistically opposite to a GLP-1 drug in an important way. Semaglutide and tirzepatide work largely by suppressing appetite, so people eat less and lose both fat and some muscle, the way any calorie deficit would. Bimagrumab does not suppress appetite. It re-partitions body composition directly at the tissue level — pushing muscle up and fat down — regardless of how much a person eats. Pairing an appetite-suppressing GLP-1 drug with a tissue-partitioning antibody is therefore a deliberate attempt to get the best of both: large total weight loss from the GLP-1 arm, and protection of the muscle that the GLP-1 arm would otherwise erode.

One practical caveat sets bimagrumab apart from the weekly pens patients have grown used to: it is delivered by intravenous infusion every several weeks rather than by a quick subcutaneous self-injection.

Inside the BELIEVE trial: bimagrumab plus semaglutide

The BELIEVE study, published in Nature Medicine in 2026 after its headline results were presented at the American Diabetes Association's 2025 Scientific Sessions, is the most important dataset on this combination to date. It was a randomized, double-blind, placebo-controlled phase 2 trial enrolling 507 adults with obesity, who were assigned across nine groups for 48 weeks of treatment.

Evidence: "In this double-blind, placebo-controlled phase 2 trial, 507 adults with obesity were randomized to nine groups to receive treatment for 48 weeks: placebo, bimagrumab (10 mg kg⁻¹ or 30 mg kg⁻¹ intravenously every 12 weeks), semaglutide (1.0 mg or 2.4 mg subcutaneously once a week) and combinations thereof." — Heymsfield SB, et al. Nature Medicine. 2026. DOI

The numbers on fat versus muscle

The total weight loss in the combination arm was striking, but the composition of that loss is the real story. The combination of bimagrumab 30 mg/kg and semaglutide 2.4 mg removed an average of 17.8 kg over 48 weeks. Semaglutide 2.4 mg alone removed 14.2 kg, and bimagrumab 30 mg/kg alone removed 9.3 kg, against just 3.3 kg with placebo. Where the arms diverged most was in what was lost.

The contrast is the entire point. Semaglutide on its own put about 28% of its weight loss into lean tissue and produced a 7.4% drop in lean mass. Bimagrumab on its own increased lean mass by roughly 2.5%. Combined, almost 93% of the weight that came off was fat.

Evidence: "Bimagrumab, an antibody that blocks activin signaling pathways, combined with semaglutide results in greater weight loss while also preserving lean mass, such as skeletal muscle and connective tissue; at the highest combination dose tested, participants lost 42% of their total body fat mass over 48 weeks, compared with 25% for semaglutide 2.4 mg alone." — Heymsfield SB, et al. Nature Medicine. 2026. DOI

Visceral fat and metabolic markers

Total fat is one measure; where the fat sits matters more for cardiometabolic risk. On that front the combination again outperformed: visceral adipose tissue fell by about 58% in the combination group versus roughly 36% with semaglutide alone. Visceral fat is the depot most tightly linked to insulin resistance, fatty liver, and cardiovascular events, so a larger reduction there is metabolically meaningful beyond the number on the scale. This is the same "quality of weight loss" argument now being made for the leanest of the GLP-1 pipeline drugs, such as the glucagon co-agonist pemvidutide — but bimagrumab pursues it from the opposite direction, building muscle rather than tuning the incretin signal.

The earlier evidence: bimagrumab in type 2 diabetes

BELIEVE did not come out of nowhere. The signal that bimagrumab could reshape body composition first appeared in a 2021 phase 2 trial in adults with type 2 diabetes and obesity. That smaller study of 75 patients ran for 48 weeks and produced an unusually clean separation between fat and muscle.

Evidence: "Among adults with type 2 diabetes and obesity, treatment with bimagrumab compared with placebo resulted in a significant decrease in total body fat mass (−20.5% vs −0.5%) and an increase in lean mass (+3.6%) over 48 weeks, with an accompanying reduction in HbA1c." — Heymsfield SB, et al. JAMA Network Open. 2021. DOI

A roughly 21% reduction in body fat with a simultaneous gain in lean mass and an improvement in blood-glucose control is a profile no appetite-suppressing drug produces on its own. It established the core hypothesis that BELIEVE then tested at scale and in combination: that you can subtract fat and add muscle at the same time.

Safety, dosing, and the open questions

Bimagrumab is not a finished product. Several caveats temper the enthusiasm:

• It is investigational. As of 2026, bimagrumab is not approved by the FDA or any major regulator for weight loss. The BELIEVE data are phase 2 — promising, but a step short of the large, long phase 3 program that approval requires.
• The route of administration is a hurdle. Intravenous infusion every several weeks is more demanding than a self-administered weekly pen, and convenience strongly shapes real-world adherence to weight-loss therapy.
• The side-effect profile is its own. Across the bimagrumab trials, the most frequently reported adverse events were mild diarrhea and muscle spasms or cramps, layered on top of the familiar gastrointestinal effects that come from the semaglutide component. These were generally mild to moderate, but long-term tolerability over years of use is unknown.
• Durability is unproven. Whether the muscle-sparing advantage persists, and whether it translates into better physical function, fewer falls, or improved weight maintenance after stopping, has not been demonstrated.

The unanswered questions are as important as the results. A 17.8 kg average loss with 93% of it from fat is a phase 2 finding in roughly 500 people over under a year. The history of obesity drugs is full of phase 2 signals that softened in phase 3, and the muscle-preservation field has competitors — myostatin inhibitors and other muscle-targeting agents are also being paired with GLP-1 drugs.

Key takeaways

Bimagrumab reframes a problem the GLP-1 era created. The current weight-loss drugs are extraordinarily effective at removing mass, but a meaningful share of that mass is muscle — and muscle is the tissue you least want to lose. By blocking activin receptors and re-partitioning the body toward muscle and away from fat, bimagrumab attacks that weakness from a completely different mechanism than appetite suppression.

The BELIEVE trial showed that combining it with semaglutide produced larger total weight loss and dramatically better body composition than semaglutide alone, with almost all of the loss coming from fat and a much larger cut to visceral fat. Until phase 3 trials confirm the benefit, establish long-term safety, and resolve the infusion-versus-injection question, the practical advice for anyone on a GLP-1 medication today remains unchanged: resistance training and adequate protein are the proven tools for protecting muscle. Bimagrumab is the clearest sign yet that pharmacology may soon add a third.

References

1. Heymsfield SB, et al. Bimagrumab and semaglutide alone or in combination for the treatment of obesity: a phase 2 randomized clinical trial. Nature Medicine. 2026;32(3):869-882. DOI: 10.1038/s41591-026-04204-0
2. Heymsfield SB, et al. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial. JAMA Network Open. 2021;4(1):e2033457. DOI: 10.1001/jamanetworkopen.2020.33457
3. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021;384(11):989-1002. DOI: 10.1056/NEJMoa2032183
4. Neeland IJ, et al. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes, Obesity and Metabolism. 2024;26(Suppl 4):16-27. DOI: 10.1111/dom.15728
5. Prado CM, et al. Muscle matters: the effects of medically induced weight loss on skeletal muscle. The Lancet Diabetes & Endocrinology. 2024;12(11):785-787. DOI: 10.1016/S2213-8587(24)00272-9

Last updated: 2026-06-13 Medical review: Dr. James Chen, MD, PhD, FACE