Pune, India | September 19, 2025
Weight loss has long been associated with an often-overlooked drawback—loss of muscle mass. While shedding excess fat can improve health, losing lean tissue may reduce strength, slow metabolism, and limit mobility. Regeneron’s Phase 2 COURAGE trial brings new hope. It suggests that patients may reduce fat while better preserving muscle.
The COURAGE trial tested whether adding experimental antibodies to semaglutide could enhance results. Semaglutide, a GLP-1 receptor agonist, is already used for obesity treatment. The study involved adults with a body mass index (BMI) of 30 or higher and lasted 26 weeks.
Researchers divided participants into four groups. One group received semaglutide alone. The others received semaglutide with trevogrumab—either in low or high doses—or combined with garetosmab. Trevogrumab blocks myostatin (GDF8), a protein that limits muscle growth. Garetosmab targets activin A, another muscle-regulating protein.
The findings revealed a clear difference between the groups. In the semaglutide-only group, about 33–35% of weight loss came from lean muscle. However, patients in the combination therapy groups preserved significantly more muscle mass.
The group receiving both antibodies retained nearly 80% of the lean mass they might have lost. They also showed greater fat reduction. This triplet therapy group lost up to 27% more fat than the semaglutide-only group. These results suggest that losing fat while keeping muscle could reshape the future of weight-loss treatment.
Most traditional weight-loss programs focus on total pounds lost. They often overlook the importance of body composition. The COURAGE trial highlights why preserving muscle is just as important as shedding fat. Muscle supports metabolism, strength, and mobility. It plays a vital role in both everyday function and long-term health.
If confirmed by larger studies, this dual-target strategy could lead to healthier outcomes. Many current treatments sacrifice muscle in the process of reducing weight.
However, the trial also raised safety concerns. As treatment complexity increased, so did side effects. The triplet therapy group had more severe adverse events and a higher dropout rate. Sadly, two participants in that group died. Investigators have not directly linked the deaths to the therapies. Still, the findings highlight the need for caution.
Balancing potential benefits with safety risks remains essential. Any future use of such therapies will require thorough review and monitoring.
The trial has now entered a second phase, lasting another 26 weeks. This phase will focus on maintaining weight loss and preserving muscle over time. Researchers will also assess how well patients tolerate the treatments during extended use.
If positive results continue, Regeneron’s approach could reshape how we treat obesity. The shift from weight loss alone to improved body composition could offer lasting health benefits. Patients might not only become leaner but also stronger and more physically capable.
The COURAGE trial marks a turning point in obesity care. It moves the goal from just losing weight to losing the right kind of weight. Smarter fat-loss strategies that protect muscle may lead to a better quality of life.
While early results are promising, more research is needed. Larger trials will help confirm these outcomes and refine the right dosing for different patients.
In summary, the COURAGE trial shows a future where obesity treatments do more than shrink the number on the scale. They may also help preserve strength, mobility, and resilience. If proven safe and effective, Regeneron’s combination therapy could lead to a new era in weight-loss science—one that promotes balance, not just loss.
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