What Reta Actually Does To Your Muscle (First DXA Data)

Retatrutide produces the largest weight loss numbers of any drug tested so far, and for the first time, researchers have scanned exactly what that weight is made of.

The Lancet just published body composition data from a substudy of the retatrutide phase 2 trial, where 103 people with type 2 diabetes had their bodies measured with DXA at the start and again at 36 weeks. DXA, which stands for dual-energy X-ray absorptiometry, is the method that separates your total body weight into its actual components: fat mass, lean mass, and bone. It is the gold standard for this kind of measurement, meaning it is more precise than what a scale or even a DEXA-alternative body scan can tell you. These are the first scans of this kind on retatrutide, and the numbers are worth understanding carefully.

At the highest dose tested, 12 milligrams, total fat mass dropped by 23.2 percent and visceral fat dropped by 31.4 percent. Visceral fat is the fat stored around your organs inside the abdominal cavity, and it is the type most strongly linked to metabolic disease, so that 31 percent reduction is a meaningful clinical outcome. Of the total weight lost, roughly 75 to 80 percent was fat and the remaining 20 to 25 percent was lean mass.

Now, that ratio is how most people will first hear this reported, and they will hear it described as reasonable. And compared to other drugs, the ratio actually is reasonable.

Tirzepatide, from the SURMOUNT-1 body composition substudy, shows almost exactly the same split: about 75 percent fat and 25 percent lean mass. Semaglutide is measurably worse on this metric, with roughly 60 percent of weight lost coming from fat and about 40 percent coming from lean tissue. So if you are comparing these three drugs purely on the ratio of fat to lean mass lost, retatrutide and tirzepatide look similar, and both look better than semaglutide.

But the ratio is only half the story, and it is the less important half.

The number that matters more is the absolute amount of lean tissue lost, because absolute loss is what determines how much muscle you are actually walking away with. And this is where the scale of retatrutide changes the calculation entirely.

In the phase 2 trial published in the New England Journal of Medicine, retatrutide at 12 milligrams produced an average weight loss of 24.2 percent of body weight at 48 weeks. If you apply the 20 to 25 percent lean mass ratio to someone losing 24 kilograms of total body weight, you get somewhere between 4.8 and 6 kilograms of lean tissue lost. That is between 10 and 13 pounds of lean mass gone, and most of that is muscle.

To put that in perspective: losing that much lean tissue would take most people years of intentional muscle building to recover, and that assumes they are training specifically to do so.

This is where a popular theory about retatrutide runs into the scan data.

Retatrutide is a triple agonist, meaning it activates three different hormone receptors: GLP-1, GIP, and the glucagon receptor. The GLP-1 and GIP mechanisms are shared with tirzepatide. The glucagon receptor is what makes retatrutide unique. And before this body composition data existed, a reasonable hypothesis was that the glucagon component would preferentially drive fat oxidation and spare lean mass, that activating the glucagon receptor would shift the body toward burning fat for fuel in a way that protected muscle.

The scan data does not support that hypothesis.

The ratio of fat lost to lean mass lost on retatrutide is no better than tirzepatide, which does not activate the glucagon receptor at all. The glucagon component appears to be contributing to the greater magnitude of total weight loss, and there is research showing that glucagon receptor activation increases the breakdown of amino acids in the liver for energy through a process called hepatic amino acid catabolism, but it does not appear to be selectively protecting muscle tissue over fat tissue the way the theory suggested.

So you are left with a drug that produces the largest weight loss numbers currently available, with a lean mass loss ratio that is comparable to its nearest competitor, which means the absolute amount of muscle at risk is the largest of any drug on the market.

The practical implication of this is direct.

Resistance training, meaning training that puts progressive mechanical load on your muscles, is the primary signal your body uses to determine whether lean tissue is worth keeping during a caloric deficit. Without that signal, the body has no strong reason to preserve muscle over fat when it needs to reduce total mass. And dietary protein provides the raw material your muscles need to maintain or rebuild their structure, with most evidence supporting somewhere around one gram per pound of goal body weight per day as a working target.

The drug produces the deficit and drives the fat loss. It does not produce the anabolic signal that tells your body to hold onto muscle. That signal has to come from somewhere else, and resistance training is the primary source of it.

The reason this matters more on retatrutide than on other GLP-1 medications is not that the drug is worse at preserving lean mass on a percentage basis. It is that the drug is so effective at producing total weight loss that the same percentage represents a much larger number of pounds of actual muscle tissue. The math scales with the magnitude of the effect.

Most people evaluating these drugs focus on total weight lost and fat percentage lost, and both of those numbers on retatrutide are the best available. But body composition is not just about what you lose. It is about what you are left with, and the muscle you carry into and out of a treatment period determines your metabolic rate, your functional capacity, and your long-term trajectory.

The strongest drug for fat loss also creates the highest absolute demand for the behaviors that protect lean tissue. That is exactly why the percentage tells only part of the story.

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References

1. Retatrutide Body Composition Substudy, 2025, The Lancet Diabetes & Endocrinology, Vol 13(8), 674-684. Phase 2, 42 centers, 103 DXA-completed participants with T2D. Fat mass reduction: 23.2% at 12mg. Lean mass: 20-25% of total weight lost. Visceral fat: -31.4% at 12mg.
2. SURMOUNT-1 Body Composition Substudy (Tirzepatide), 2025, Lancet Diabetes Endocrinol. PMC11965027. ~75% fat / 25% lean mass ratio.
3. STEP 1 Body Composition Substudy (Semaglutide), PMC8089287. ~60% fat / 40% lean mass ratio.
4. Jastreboff et al., 2023, NEJM. Retatrutide phase 2 trial (N=338): 24.2% weight loss at 48 weeks (12mg). DOI: 10.1056/NEJMoa2301972.
5. Sherwood et al., 2022, Cell Reports Medicine. GCGR activation upregulates hepatic amino acid catabolism, coupled to energy expenditure increase. PMC9729826.

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