Phase 2 COURAGE Trial Confirms Trevogrumab Prevents Lean Mass and Muscle Loss During GLP-1 Receptor Agonist-induced Weight Loss
Muscle preservation persisted through 52 weeks, while lower-dose trevogrumab did not meaningfully enhance semaglutide-associated weight loss.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Regeneron Pharmaceuticals (NASDAQ: REGN) reported Phase 2 COURAGE results showing trevogrumab preserved muscle during semaglutide-induced weight loss in people with obesity. At the 52-week primary endpoint, lean mass fell 5.8% with 25 mg trevogrumab and 4.2% with 75 mg, versus 7.3% with placebo, all combined with semaglutide. Relative lean mass preservation was 20.5% and 42.5%, respectively.
Among participants with evaluable MRI scans, thigh muscle preservation at 52 weeks was 71.8% and 68.9%, respectively, relative to placebo plus semaglutide. Lower-dose trevogrumab did not meaningfully enhance weight loss. Adverse events occurred in 77% of trevogrumab participants versus 82% with placebo. Participants with low baseline lean mass showed numerically greater preservation with trevogrumab. Regeneron plans another Phase 2 trial in older adults with obesity and decreased muscle mass and/or strength.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Hollow bars mark forward-looking points. How the balance works
Positive
- Moderate pointTrevogrumab 75 mg preserved 50.7% of lean mass loss at 26 weeks and 42.5% at 52 weeks versus placebo plus semaglutide.
- Minor pointTrevogrumab 25 mg preserved 29.9% of lean mass loss at 26 weeks and 20.5% at 52 weeks versus placebo plus semaglutide.
- Minor pointMRI-evaluable participants receiving 25 mg had 63.6% thigh muscle preservation at 26 weeks and 71.8% at 52 weeks versus placebo plus semaglutide.
- Minor pointMRI-evaluable participants receiving 75 mg had 72.7% thigh muscle preservation at 26 weeks and 68.9% at 52 weeks versus placebo plus semaglutide.
- Minor pointAdverse-event incidence with lower-dose trevogrumab was 77%, compared with 82% among placebo-treated participants.
2 minor points
- Minor pointLow-baseline-lean-mass participants showed numerically greater lean mass preservation with trevogrumab than participants without low baseline lean mass.
- Minor point. Forward-looking: it has not happened yet and may not happen.Regeneron plans a Phase 2 trial combining trevogrumab with GLP-1-based therapies in older adults with obesity and decreased muscle mass and/or strength.
Negative
- Moderate pointLower-dose trevogrumab did not meaningfully enhance weight loss achieved with semaglutide alone.
- Minor pointCommon adverse events occurring in ≥10% of patients included nausea, constipation, diarrhea and vomiting.
AI-generated analysis. How Rhea-AI works. Not financial advice.
In a predefined MRI substudy, trevogrumab prevented
A pre-specified subgroup analysis found that patients meeting the low lean mass definition for sarcopenia had greater loss of lean mass with semaglutide, and more preservation with trevogrumab
Findings were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting and is in press with The Lancet
TARRYTOWN, N.Y., Oct. 01, 2026 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced new results from the Phase 2 COURAGE trial evaluating trevogrumab (anti-GDF8/anti-myostatin) for its potential to prevent lean mass and muscle loss during GLP-1 receptor agonist-induced weight loss in people living with obesity. The results of the trial were presented during a Scientific Symposium at the European Association for the Study of Diabetes (EASD) Annual Meeting and is in press with The Lancet. Building on these positive findings, Regeneron is planning to initiate a Phase 2 trial evaluating trevogrumab in combination with GLP-1 receptor agonist-based therapies in older adults with obesity and decreased muscle mass and/or strength.
“COURAGE demonstrated that trevogrumab, which blocks myostatin, can preserve lean mass and muscle during semaglutide-induced weight loss,” said Julio Rosenstock, M.D., Lead Principal Investigator of the COURAGE trial and Clinical Professor of Medicine, University of Texas Southwestern Medical Center, Dallas. “These results, sustained through a full year of treatment, were further validated by MRI measurements of muscle volume supporting continued clinical development of trevogrumab and future research into muscle preservation as part of obesity care.”
COURAGE investigated the quality of weight loss in people living with obesity (BMI ≥30 kg/m2) in two independent portions over 52 weeks. A higher-dose portion evaluated trevogrumab (200 mg or 400 mg) in combination with semaglutide 2.4 mg for 26 weeks compared to semaglutide alone, and then trevogrumab compared to placebo alone for an additional 26 weeks after semaglutide was discontinued. The trial also included a treatment arm with semaglutide, trevogrumab and an Activin-A inhibitor for which the results were previously presented.
A lower-dose portion evaluated trevogrumab (25 mg or 75 mg) in combination with semaglutide 2.4 mg compared to semaglutide monotherapy for 52 weeks. The results in this portion replicated the findings of the higher-dose portion, with the greatest reduction in lean mass occurring during the period of most rapid weight loss that was observed in the first six months of treatment. While lower-dose trevogrumab did not meaningfully enhance the weight loss achieved with semaglutide alone, it preserved lean mass at both 26 and 52 weeks (the primary endpoint), compared to placebo, as outlined in the table below:
| Percent change in lean mass from baseline as measured by DXA | ||
| Arm | 26 weeks | 52 weeks |
| Placebo + semaglutide | - | - |
| Trevogrumab 25 mg + semaglutide | - | - |
| Trevogrumab 75 mg + semaglutide | - | - |
*Relative to placebo + semaglutide
Among participants with evaluable MRI data, lower dose trevogrumab preserved almost
| Absolute change from baseline in fat free muscle volume (mean ± standard error) as measured by MRI | ||
| Arm | 26 weeks | 52 weeks |
| Placebo + semaglutide | -0.88 ± 0.21 | -1.03 ± 0.22 |
| Trevogrumab 25 mg + semaglutide | -0.32 ± 0.14 | -0.29 ± 0.12 |
| Trevogrumab 75 mg + semaglutide | -0.24 ± 0.13 | -0.32 ± 0.13 |
*Relative to placebo + semaglutide
The lower doses of trevogrumab were generally well tolerated, with
Also presented at EASD was a pre-specified subgroup analysis of participants with low lean mass (LLM) at baseline. Compared to patients without LLM at baseline, these patients experienced a greater loss of lean mass with semaglutide alone and numerically more preservation of lean mass in combination with trevogrumab. LLM was defined using the imaging component of the sarcopenia definition established by the Foundation for the National Institutes of Health (appendicular lean mass relative to BMI, measured by DXA).
“As GLP-1 receptor agonist-based medicines become foundational to obesity care, it is becoming increasingly recognized that the associated muscle loss is an increasing concern – particularly for people with sarcopenia, older adults and others where frailty is a real concern,” said Boaz Hirshberg, M.D., Senior Vice President, Clinical Development, Internal Medicine, Regeneron. “Our COURAGE trial not only confirms this concern about muscle loss but also shows that trevogrumab can be part of the solution, addressing not the quantity, but rather the quality, of weight loss. It’s an approach we’re building across our growing pipeline.”
Additionally, Hansoh presented data from their Phase 3 trial in Chinese patients evaluating olatorepatide for the treatment of adults with obesity or who are overweight. Olatorepatide is a novel GLP-1/GIP receptor agonist for which Regeneron has exclusive clinical development and commercial rights outside of the Chinese Mainland, Hong Kong and Macau as part of a strategic in-licensing agreement.
The safety and efficacy of trevogrumab and olatorepatide have not been evaluated by any regulatory authority.
About Regeneron in Obesity
Obesity is a complex, multifaceted disease and a growing public health concern that affects more than a billion people worldwide. Despite the revolutionary impact of GLP-1 receptor agonists (GLP-1RAs) on weight loss, the quality of this weight loss can be negatively impacted because these agents can cause profound muscle loss.
At Regeneron, we are developing a pipeline focused on the quality of weight reduction. We have several independent approaches focused on promoting and preserving muscle during weight loss, so as to increase the amount of fat loss since adiposity is the principal driver of comorbidities and metabolic diseases associated with obesity. In addition, Regeneron has an extensive pipeline of agents to address some of these co-morbidities and metabolic diseases, which have the potential to be combined with GLP-1RAs. The combination of our science, pipeline, research and clinical innovation uniquely positions us to make a meaningful difference in obesity and obesity-related diseases.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.
Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.
For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.
Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation the clinical programs discussed or referenced in this press release evaluating trevogrumab (anti-GDF8/anti-myostatin) in combination with semaglutide or other GLP-1 receptor agonist-based therapies to prevent lean mass and muscle loss during GLP-1 receptor agonist-induced weight loss as well as olatorepatide as a monotherapy for the treatment of adults with obesity or who are overweight; uncertainty of the utilization, market acceptance, and/or commercial success of Regeneron’s Products and Regeneron’s Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products and Regeneron’s Product Candidates (such as those referenced above); 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A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2025 and its Form 10-Q for the quarterly period ended June 30, 2026. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.
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| Media Relations Mary Heather Tel: +1 914-847-8650 mary.heather@regeneron.com | Investor Relations Matthew Feeney Tel: +1 914-847-1004 matthew.feeney@regeneron.com |
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What did Regeneron's COURAGE trial show at the 52-week primary endpoint?
Lean mass declined 5.8% with 25 mg trevogrumab and 4.2% with 75 mg, versus 7.3% with placebo, all combined with semaglutide. These results represented 20.5% and 42.5% lean mass preservation, respectively, relative to placebo plus semaglutide. Lean mass was measured using DXA, an imaging method.
How did the higher-dose and lower-dose portions of Regeneron's COURAGE trial differ?
The higher-dose portion used 200 mg or 400 mg trevogrumab, while the lower-dose portion used 25 mg or 75 mg. Higher-dose participants received combination treatment with semaglutide 2.4 mg for 26 weeks, followed by trevogrumab versus placebo for another 26 weeks after semaglutide stopped. The lower-dose portion compared combination treatment with semaglutide monotherapy over 52 weeks.
How was low lean mass defined in Regeneron's COURAGE subgroup analysis?
Low lean mass used the imaging component of the Foundation for the National Institutes of Health sarcopenia definition: appendicular lean mass relative to BMI, measured by DXA. Participants meeting this definition lost more lean mass with semaglutide alone than those without low baseline lean mass.