COURAGE update reports muscle preservation with trevogrumab during semaglutide treatment

Regeneron on October 1 reported new COURAGE trial findings suggesting that its experimental antibody trevogrumab reduces muscle loss during semaglutide treatment for obesity. The update addresses a question relevant to healthy aging: whether drug-assisted weight loss can preserve tissue needed for physical function.

The results were presented at the European Association for the Study of Diabetes meeting in Milan, following a September 30 conference announcement. They provide evidence about body composition, while leaving the effects on strength, mobility and disability unresolved.

What the trial tested

The conference report describes two randomized Phase 2 comparisons in adults with obesity, defined by a body mass index of at least 30. Trevogrumab blocks myostatin, a protein that restrains muscle growth. It is an antibody being studied alongside the peptide medicine semaglutide.

A higher-dose portion enrolled 599 participants and assessed treatment combinations over 26 weeks, followed by a semaglutide-withdrawal period. A separate lower-dose portion enrolled 376 participants who received semaglutide alongside either trevogrumab or placebo for 52 weeks. Primary outcomes included percentage changes in lean mass, fat mass and body weight.

These distinctions matter when comparing headlines: results from different treatment groups, follow-up periods and imaging methods describe different aspects of the response.

Less tissue loss, with limits

In the sponsor's lower-dose comparison, lean mass measured by dual-energy X-ray absorptiometry declined 7.3% with placebo plus semaglutide at 52 weeks. The corresponding declines in the two trevogrumab groups were 5.8% and 4.2%. Lower-dose trevogrumab did not meaningfully increase overall weight loss.

Among participants with evaluable MRI scans, the company reported approximately 70% less loss of thigh muscle volume with trevogrumab relative to the comparator. That percentage describes a reduction in the amount lost; it does not mean participants gained 70% more muscle.

The announcement did not provide the MRI subgroup's size alongside its results table. That limits assessment of how representative the imaging findings are. Regeneron described the research as in press with The Lancet; the available announcement should not be treated as a substitute for an independently examined full paper.

Safety depends on the combination

Reuters reported that an earlier three-drug group, which also included the antibody garetosmab, had substantial tolerability problems, including muscle spasms. Two participants in that group died during the initial 26 weeks. Those events do not, by themselves, establish that treatment caused the deaths.

According to Reuters, Regeneron will not advance that triple combination. Its safety experience must be distinguished from the two-drug approach, but remains relevant to interpreting the broader development program. Encouraging body-composition measurements alone cannot establish an acceptable balance of benefits and harms.

The healthspan question remains open

Established European consensus guidance places low muscle strength at the center of sarcopenia assessment, using low muscle quantity or quality to confirm the diagnosis and poor physical performance to identify severe disease. This provides a useful framework for interpreting COURAGE: preserving tissue is an intermediate finding, whereas maintaining the ability to move and function is the clinical goal.

A favorable scan therefore cannot establish fewer falls, less disability or longer independent living. Those outcomes require direct testing, particularly in older people with limited muscle reserve.

Reuters reports that Regeneron plans further study in people over 65. Such research could help determine whether the body-composition signal translates into meaningful functional benefit. For now, trevogrumab remains an investigational approach whose practical value depends on stronger evidence about function, durability and safety.