By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
The COURAGE trial: why it matters to anyone on weight loss injections
The COURAGE trial tackles a question many patients ask: can you lose weight without losing muscle? Over the past decade, GLP-1 drugs have transformed obesity medicine. Semaglutide, the active ingredient in Wegovy, lowers weight, improves blood sugar control and reduces cardiovascular risk. Yet alongside this success, an important question has emerged. What exactly are we losing along the way? Is it only fat, or muscle too?
This is where a new study by Regeneron comes in. It does not just measure the problem with great precision. In addition, it tests a drug-based solution that may mark the next generation of obesity treatment.
The silent problem of rapid weight loss
Weight loss, even under medical supervision, usually includes some loss of lean body mass. Lean mass is everything that is not fat: muscle, organs, bone and water. However, muscle does far more than shape how we look. Indeed, it is active metabolic tissue that supports a healthy metabolism, strength and daily function. What’s more, it helps you keep weight off over time.
So how much muscle do people actually lose? The answer, however, varies from study to study. A review in the journal Diabetes, Obesity and Metabolism found a wide range. In some studies, lean mass made up 40% to 60% of the weight lost, while in others it was about 15% or less. For example, in the SURMOUNT-1 body composition substudy with tirzepatide, about 75% of the weight lost was fat and about 25% was lean mass. You can find more on this topic in my article on GLP-1 drugs and muscle mass.
What the COURAGE trial tested
The COURAGE trial is a phase 2 study that tested a new approach: combining semaglutide with biologic antibodies designed to protect muscle. The researchers tested two antibodies:
- Trevogrumab, which blocks myostatin, a protein that limits muscle growth.
- Garetosmab, which blocks activin A, a protein that also acts as a brake on muscle building.
Thus, both proteins act as a kind of brake in the body. So when you block them, the body should preserve much more muscle even as weight comes down. The trial enrolled adults with obesity (a BMI of 30 or higher), who received semaglutide alone or combined with the antibodies.
Interim COURAGE trial results: how much muscle the treatment preserved
In June 2025, Regeneron released interim results from the COURAGE trial after 26 weeks. In the semaglutide-only group, 34.5% of the weight lost was lean mass. That works out to an average loss of 7.9 pounds, about 3.6 kg, in just six months.
By contrast, the combination with trevogrumab preserved about 51% of the lean mass lost on standard treatment (50.8% at the low dose and 51.3% at the high dose). The triple combination, with garetosmab, preserved 80.9% of that lean mass. This group also had the largest fat loss: 13.2% of body weight, compared with 10.4% on semaglutide alone. Put simply, you can lose a lot of fat and pay a much smaller price in muscle.
Full results of the COURAGE trial
At the European Association for the Study of Diabetes (EASD) meeting in late September 2026, the researchers presented the full data. According to a report on Healio, the first part of the trial included 599 adults. After 26 weeks, the semaglutide-only group lost 3.4 kg of lean mass. In comparison, the groups on trevogrumab combinations lost only 1.6 to 1.9 kg. Meanwhile, total weight loss was similar across all groups.
The second part included 376 adults, and treatment lasted a year. Lean mass fell by 7.3% on semaglutide alone, compared with 5.8% and 4.2% on low doses of trevogrumab. Interestingly, patients who started with low lean mass lost especially large amounts of muscle on semaglutide alone. Yet in exactly this group, adding the antibody gave muscle particularly strong protection.
The other side: safety and clinical meaning
As with any novel treatment, there are caveats here too. The triple combination came with a high rate of side effects. In the interim results, 28.3% of patients in this arm stopped treatment because of side effects, compared with 4.6% on semaglutide alone. In addition, two deaths occurred in the triple arm. However, the company reported that it found no causal link to the treatment. Following this, Regeneron decided not to advance the triple combination.
On the other hand, semaglutide combined with trevogrumab alone was generally well tolerated. Still, one notable side effect was muscle cramps. Keep in mind that no regulatory agency has approved these antibodies yet. In other words, this is a promising research direction, not yet a treatment you can get in the clinic.
Not just Regeneron: more drugs to preserve muscle
The COURAGE trial is not alone in this field. In Lilly’s BELIEVE study, semaglutide was combined with the antibody bimagrumab. According to an American Diabetes Association press release, the combination led to 22.1% weight loss, compared with 15.7% on semaglutide alone. What’s more, 92.8% of the weight lost on the combination was fat, compared with 71.8% on semaglutide alone. You can read about the next drugs in this field in my article on new obesity drugs.
What the COURAGE trial tells patients today
The study highlights a deep shift in thinking. Weight loss is not a goal in itself; body composition is the real target. After all, preserving muscle means less weakness and less fatigue. In addition, it supports a stable metabolism and the ability to maintain results over time. This message matters most for older adults, women after menopause and patients prone to muscle wasting.
Until drugs like these are approved, we already have proven tools. The joint recommendations of four American organizations suggest strength training at least three times a week, along with 150 minutes of aerobic activity. They also suggest a high protein target, for example 1.2 to 1.6 grams per kilogram per day during active weight loss. For practical details, see my protein intake guide and my article on aerobic vs. strength training.
Looking ahead: obesity medicine in the coming years
In the near future, the key question in obesity treatment will no longer be just how many kilograms came off. Instead, we will ask three questions:
- How much fat did you lose?
- How much muscle did you manage to keep?
- What effect did the change have on your quality of life?
Ultimately, the COURAGE trial is among the first to lay the groundwork for precision obesity medicine. Specifically, this is medicine that sees the body as a whole, not just the number on the scale. In our clinic, we already work this way, through personalized obesity treatment that combines medication, nutrition and exercise.
The information in this article is general and does not replace personal medical advice.
References
Monoclonal antibody combined with Wegovy helps preserve lean mass with obesity treatment
Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies
New GLP-1 Therapies Enhance Quality of Weight Loss by Improving Muscle Preservation
The COURAGE trial is funded by Regeneron, and the BELIEVE study by Lilly.
