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

Retatrutide loses weight faster than any other drug currently in clinical use, and that speed is exactly what makes the new body composition data worth understanding carefully.

The Lancet just published the first DXA scan data on retatrutide in people with type 2 diabetes. DXA, which stands for dual-energy X-ray absorptiometry, is the method researchers use when they want to know not just how much weight someone lost but what kind of weight. Fat versus muscle. The study scanned 103 people at the start and again at 36 weeks, and the numbers are specific enough to tell you something meaningful about what this drug actually does inside your body.

Before getting into the body composition split, it helps to understand why retatrutide was expected to be different from everything before it.

Most GLP-1 drugs work on a single receptor. GLP-1 is a gut hormone that tells your pancreas to release insulin, slows how fast food leaves your stomach, and sends satiety signals to your brain. Semaglutide and liraglutide are essentially precision tools aimed at that one receptor. Tirzepatide added a second receptor, GIP, which appears to amplify the GLP-1 effect and improve how the body handles fat. Retatrutide goes one step further and adds a third receptor: the glucagon receptor.

Glucagon is the hormone that does the opposite of insulin. When blood sugar drops, glucagon tells your liver to release stored glucose and ramp up energy production. But glucagon also does something in the context of fat metabolism that made researchers optimistic about retatrutide specifically: it increases thermogenesis, which is heat production from burning fuel, and it was theorized to shift that fuel preference toward fat oxidation rather than breaking down muscle tissue.

The logic was reasonable. If the glucagon component pushes your body to burn fat for energy at a higher rate, then a larger fraction of the weight you lose should come from fat, and your lean mass should be relatively protected. That was the theory going into this study.

The DXA data tells a different story.

At the 12 milligram dose, total fat mass dropped by 23.2 percent and visceral fat, which is the fat stored around your internal organs and the kind most associated with metabolic disease, dropped by 31.4 percent. Those are meaningful reductions. But when you look at the ratio of what was lost, roughly 75 to 80 percent of total weight lost was fat and 20 to 25 percent was lean mass. That ratio is almost identical to tirzepatide, which also lands around 75 percent fat to 25 percent lean in its own body composition substudy. Semaglutide performs worse on this measure, losing roughly 60 percent fat and 40 percent lean, so retatrutide and tirzepatide are both more favorable than semaglutide in terms of how the weight loss is distributed.

But ratios can be misleading, and this is where the math becomes important.

The same phase 2 trial data showed an average weight loss of about 24 kilograms at the 12 milligram dose over 48 weeks, which is the largest weight loss number ever recorded for a pharmacological intervention. When you apply that 20 to 25 percent lean mass figure to 24 kilograms of total loss, you get somewhere between 4.8 and 6 kilograms of lean tissue lost. That is 10 to 13 pounds of muscle and structural tissue gone over the course of the treatment.

The percentage looks acceptable. The absolute number is substantial.

This is a different kind of problem than the one semaglutide presents. Semaglutide has a worse ratio, meaning a higher fraction of your losses come from lean mass, but the total weight lost is smaller, so the absolute amount of lean mass lost ends up being lower than what you see with retatrutide at the high dose. Retatrutide's size advantage as a weight loss agent is also its liability when it comes to muscle preservation.

Now, back to the glucagon receptor. Research published in Cell Reports Medicine showed that glucagon receptor activation does upregulate something called hepatic amino acid catabolism, which is the process by which your liver breaks down amino acids from protein for energy. This is one mechanism by which the glucagon component could actually accelerate lean mass loss rather than prevent it, because if your liver is clearing amino acids from circulation faster, there is less raw material available for muscle protein synthesis and repair. This remains a theoretical concern based on mechanism rather than a finding directly proven in the human body composition data, but it is worth understanding as context for why the glucagon receptor did not produce the lean mass protection that was initially hoped for.

So what does this mean practically.

The drug will reduce fat mass aggressively and it will reduce visceral fat in particular at a rate that no other approved compound matches. But the drug does not distinguish between the fat you want gone and the muscle you want to keep. That job belongs to resistance training and dietary protein, and at the doses where retatrutide produces its most dramatic results, the stakes for getting those two things right are higher than with any other medication in this class.

Resistance training three to five times per week gives your muscles a reason to exist under the conditions of a significant caloric deficit. When your body is operating with less incoming fuel, it makes decisions about what to maintain and what to break down, and mechanical tension from training is the primary signal that tells it to maintain muscle tissue. Without that signal, the lean mass losses documented in this trial become the default outcome.

Protein intake operates on the same principle. Somewhere around one gram per pound of your goal body weight gives your body enough amino acids to support muscle protein synthesis even when total calories are reduced, which counteracts one of the mechanisms through which the glucagon component may be accelerating lean mass loss in the first place.

The people who will look different at the end of a retatrutide cycle compared to the people who simply lost a lot of weight are the ones who treated the muscle preservation side as seriously as the drug itself.

Retatrutide is not more powerful than its predecessors because it found a way to spare your muscle better. It is more powerful because it removes more total mass. What that mass is made of is still largely up to you.

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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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