92.6% Fat Loss! Regeneron's Trevogrumab Triple Combination Therapy Shows Significant Fat Reduction and Muscle Preservation in Phase 2 Trial

On September 17, 2025, Regeneron announced the full data from its Phase 2 clinical trial COURAGE, further demonstratingThe Potential Improvement of Semaglutide Combined with Trevogrumab (Anti-GDF8/Anti-Myostatin Antibody) on Weight Loss Quality.

The complete 26-week data are consistent with the previous interim data, showing that Trevogrumab (with or without garetosmab)Effectively slowed the lean body mass loss induced by semaglutide.

The study found that approximately 33% of the weight loss induced by semaglutide originated from lean body mass reduction, and after combining with garetosmab (anti-activin A),Triple Combination Therapy (Semaglutide + Trevogrumab + Garetosmab) Demonstrates Significant Advantages in Fat Reduction and Muscle Gain, Preventing Approximately

50% of Semaglutide-Induced Lean Body Mass Loss. This result was released in September 2025 at the 61st Annual Meeting of the European Association for the Study of Diabetes (EASD).

The COURAGE trial aims to study weight loss quality in obese patients (BMI≥30 kg/m²). The treatment is divided into two 26-week phases, including a weight loss phase and a weight maintenance phase.

During the weight-loss phase, patients were randomly assigned to receive either 2.4 mg of semaglutide monotherapy, or combination therapy with different doses of Trevogrumab (200 mg low dose, 400 mg high dose), or triple therapy with high-dose Trevogrumab and 10 mg/kg garetosmab.

According to the final analysis,The triple therapy group had the least lean body mass loss.,仅为-2.0%（-0.9 kg）,相比之下，单用司美格鲁肽组的瘦体重流失为-6.5%（-3.3 kg）。低剂量和高剂量Trevogrumab联合治疗组的瘦体重流失也明显低于单药治疗组。

In terms of fat reductionMonotherapy with semaglutide resulted in a fat loss of 15.7 pounds (67%), while the low-dose and high-dose groups receiving semaglutide in combination with Trevogrumab achieved fat losses of 17.3 pounds and 19.1 pounds, representing 83.2% and 81.9%, respectively. The triple combination therapy group achieved a fat loss of 27.1 pounds, accounting for an impressive 92.6%.

These results indicate that,The combination of Semaglutide and Trevogrumab not only effectively promotes fat reduction but also helps maintain lean body mass, thereby optimizing the quality of weight loss.

Detailed Analysis Results from Baseline to Week 26

In addition, the trial also observed significant improvements in metabolic and lipid parameters across all treatment groups, with waist circumference, blood pressure, cholesterol, triglycerides, and A1C all showing improvement.Semaglutide and Trevogrumab Combination Therapy Shows Good ToleranceCommon adverse events (≥5% incidence) include muscle spasms, nausea, constipation, fatigue, diarrhea, headache, vomiting, gastroesophageal reflux, upper respiratory tract infection, etc., and most of them are mild to moderate.

However, consistent with the interim data,The triple therapy regimen had poor tolerability and a higher rate of discontinuation due to other adverse events.

In this group, there were two deaths, one of which was a patient with multiple cardiovascular risk factors who died of unknown causes, and the other was a patient with a history of cardiovascular disease who died of cardiac arrest. Regeneron has not confirmed a causal relationship between the treatment and these deaths.

After 26 weeks, patients entered the weight maintenance phase, receiving either a higher dose of Trevogrumab monotherapy or placebo until the end of the trial (Week 52). Further studies are needed in the future to evaluate the safety and long-term effects of this combination therapy.

In summary, the COURAGE trial provides key data on maintaining lean body mass through combination therapy, especially in the field of obesity treatment. The combination of Trevogrumab and semaglutide has shown great potential. Despite some tolerability issues, this study offers valuable insights for further clinical exploration and lays the foundation for the development of safer and more effective weight-loss treatment options.

Summary

It is worth mentioning that in June this year, Regeneron reached a cooperation agreement with Hansoh Pharma, obtaining the global exclusive license for the GLP-1/GIP receptor agonist HS-20094. This new drug will also provide more possibilities for future obesity treatment. Combined with the previously published COURAGE trial data, Regeneron's innovation and progress in the weight loss field are highly anticipated.

       Title: 92.6% Fat Reduction! Regeneron's Trevogrumab Triple Combination Therapy Phase 2 Trial Shows Significant Fat Loss and Muscle Gain