LONGEVITY UNDER THE MICROSCOPE

The first generation taught us how to lose weight. The next may try to decide what the body is allowed to lose.

GLP-1 Changed Weight Loss. Now the Goal Is Changing Again

Only a few years ago, losing 15 or 20 percent of body weight with medication sounded extraordinary. GLP-1-based drugs changed that almost overnight. Semaglutide turned medical weight loss into a global phenomenon, while newer compounds have pushed expectations even further. GLP-1 drugs made major weight loss possible without bariatric surgery for many people, and retatrutide, which targets GLP-1, GIP and glucagon receptors, represents another step in that race. But tomorrow's obesity drugs may be judged by a very different question. Not simply: How much weight did you lose? But: What exactly did you lose?

The Problem Hidden Inside Spectacular Weight Loss

The human body does not conveniently remove only the tissue we dislike. During substantial weight loss, fat disappears, but lean tissue can disappear with it. That matters because muscle is not excess baggage. It is metabolically active tissue involved in glucose disposal, movement, strength and the physical reserve we depend on as we age. Appetite-suppressing medications can add another practical challenge: some people simply find it difficult to eat enough food, including enough protein, when hunger has dramatically declined. Resistance training and adequate protein therefore become particularly important during major weight loss.

“Ozempic Face” Is the Visible Part of a Bigger Story

The popular expression “Ozempic face” describes the gaunt or aged appearance some people notice after substantial weight loss. It is not a unique toxic effect of Ozempic. Rapid loss of subcutaneous facial fat can reduce facial volume, making cheeks appear hollow and skin looser. The same thing can happen after major weight loss without medication. But while changes in the face are immediately visible, changes in lean tissue elsewhere in the body are much easier to miss. The mirror notices your cheeks. It does not provide a DXA scan of your legs.

Meet Bimagrumab

This is where a very different experimental drug becomes interesting. Bimagrumab, also known as LY3985863, is not another appetite suppressant. It is a monoclonal antibody that targets type II activin receptors, part of a biological signaling system that includes activin and myostatin pathways involved in regulating skeletal muscle growth. Block the signal, and the biological equation changes. Instead of asking the body merely to eat less, researchers are attempting to influence which tissues are preserved or lost.

The 2026 Trial Produced Remarkable Numbers

The BELIEVE phase 2 trial, published in Nature Medicine in 2026, randomized 507 adults with obesity or overweight plus an obesity-related complication, but without diabetes, to placebo, bimagrumab, semaglutide or combinations of the two. After 72 weeks, high-dose bimagrumab plus semaglutide produced an average body-weight reduction of 22.1 percent. Semaglutide alone produced 15.7 percent. But body weight was not the most interesting result.

Look at the Fat, Not Just the Kilograms

At 72 weeks, total body fat mass fell by 27.8 percent with semaglutide alone. Bimagrumab alone reduced fat mass by a similar 28.5 percent despite producing less total weight loss. Combine high-dose bimagrumab with semaglutide and fat mass fell by an extraordinary 45.7 percent. Estimated visceral adipose tissue—the metabolically important fat stored around abdominal organs—fell by 35.8 percent with semaglutide, 45.1 percent with bimagrumab and 58.2 percent with the high-dose combination. Suddenly the bathroom scale begins to look like a rather primitive instrument.

And Then There Is the Muscle

Here the difference becomes difficult to ignore. Total lean mass declined by 7.4 percent with semaglutide alone after 72 weeks. With the high-dose combination, the decline was only 2.9 percent. Most strikingly, bimagrumab alone increased measured lean mass by 2.5 percent while simultaneously reducing fat mass by 28.5 percent. At week 48, researchers calculated that 71.1 percent of the weight lost with high-dose semaglutide came from fat. With the high-dose combination, the figure was 92.3 percent. Bimagrumab alone reached 100 percent in that analysis.

This Wasn't a Study of People Living on Protein Shakes

There is an important detail behind those numbers. Participants received monthly lifestyle counseling, were instructed to consume at least 1.2 grams of protein per kilogram of body weight per day and were encouraged to perform at least 150 minutes of physical activity per week. In other words, researchers were not comparing the drugs in people who had been told to ignore nutrition and movement. Yet substantial differences in lean mass still emerged. That makes the body-composition results particularly interesting.

But Does More Lean Mass Mean More Muscle?

Not automatically. This is where enthusiasm needs brakes. DXA measures lean mass, which is not identical to functional skeletal muscle. The study did not show a significant improvement in grip strength, and the researchers themselves argue that future trials should use methods such as MRI to characterize muscle volume and quality more precisely. A drug that increases a DXA lean-mass number has not yet proved that it makes someone stronger, more mobile or more resistant to age-related frailty. Biology has an irritating habit of being more complicated than the headline.

Why This Could Matter More After 40

For a young adult, unnecessary loss of muscle during dieting is already undesirable. As we move through midlife and beyond, it becomes increasingly difficult to dismiss. Muscle and strength naturally tend to decline with age, while resistance training becomes one of the most effective tools we have for preserving physical function. Deliberately losing additional lean tissue while trying to improve health creates an obvious contradiction. If an “anti-aging” strategy unnecessarily removes part of the muscle reserve we will need later in life, perhaps we should stop calling it anti-aging. It starts looking remarkably like pro-aging.

The Next Race May Be About Better Weight Loss

Bimagrumab is not alone. Researchers are investigating several approaches involving myostatin and activin signaling in an attempt to preserve muscle during major weight loss. Lilly is also testing bimagrumab with tirzepatide in a separate phase 2 trial involving adults with obesity or overweight. That study is scheduled to continue into 2027. The direction of travel is becoming clear: pharmaceutical research is beginning to treat body composition as an outcome in its own right rather than accepting every lost kilogram as equally desirable.

This Is Still Experimental Medicine

None of this means that bimagrumab is ready to become the next gym accessory. It remains investigational. Phase 2 results are not the same as proof of long-term clinical benefit, and adverse effects occurred. Muscle spasms, diarrhea and acne were among the common events associated with bimagrumab, while semaglutide produced the gastrointestinal effects already familiar from incretin therapy. We also do not yet know whether preserving or increasing lean mass pharmacologically will translate into better strength, fewer falls, greater independence or longer life. Those are much harder endpoints than a DXA scan.

Tomorrow's Scale May Need More Than One Number

The most important lesson may ultimately have little to do with one drug. GLP-1 medications forced medicine to rethink what was possible in obesity treatment. Retatrutide and other multi-agonists are pushing the magnitude of weight loss further. Bimagrumab introduces another possibility: perhaps the next breakthrough is not simply making people lighter. Perhaps it is changing the composition of what they lose.

For decades, successful dieting has been celebrated with a single number on a scale. The emerging science suggests that this may be the wrong scoreboard. Losing visceral and total body fat while preserving muscle is biologically different from losing the same number of kilograms with substantial lean tissue loss. For someone thinking about metabolic health, strength and longevity, that distinction could become increasingly important.

The first generation taught us how to lose weight. The next may try to decide what the body is allowed to lose.

References

Heymsfield SB et al. Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial. Nature Medicine. 2026. | BELIEVE Trial, NCT05616013. | Eli Lilly and Company. Phase 2 study of bimagrumab and tirzepatide, alone or in combination, NCT06643728.