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

Retatrutide is losing more total body weight than any GLP-1 drug on the market, and that fact changes how you have to read the body composition numbers that just came out of The Lancet.

To understand why, you need the full picture first.

When you take a drug that acts on the GLP-1 receptor, it slows gastric emptying and reduces appetite, so you eat less, and your body starts pulling energy from stored tissue to make up the deficit. The question every researcher and every patient wants answered is: which tissue? Fat, ideally. But the body does not only pull from fat when it is in a deficit. It pulls from lean mass too, and the ratio between those two depends on the drug, the dose, the protein intake, and the training stimulus you give your muscles.

That ratio is exactly what the new Lancet data measures.

The study put 103 people with type 2 diabetes through DXA scans, which is something called dual-energy X-ray absorptiometry, a method that bounces two different X-ray beams through your body to calculate the density of different tissues and separate your total weight into fat mass, lean mass, and bone. It is the gold standard for this kind of measurement because it does not rely on estimates the way bioelectrical impedance does. You get an actual picture of the compartments.

At baseline and again at 36 weeks, the scans tracked what happened to each compartment as participants lost weight on retatrutide.

At the 12 milligram dose, total fat mass dropped by 23.2 percent and visceral fat, which is the fat packed around your liver, pancreas, and gut rather than stored under the skin, dropped by 31.4 percent. Of the total weight lost, roughly 75 to 80 percent came from fat and the remaining 20 to 25 percent came from lean mass.

That ratio is actually reasonable by the standards of this drug class. Tirzepatide, which hits GLP-1 and GIP receptors, comes in at about 75 percent fat and 25 percent lean. Semaglutide, which only targets GLP-1, is worse at roughly 60 percent fat and 40 percent lean. So by the percentage metric alone, retatrutide looks like it is doing a good job preserving lean tissue relative to fat loss.

But this is where the math stops being comfortable.

Retatrutide at 12 milligrams produces around 24 kilograms of total weight loss over 48 weeks based on the phase 2 trial data. When you take 20 to 25 percent of 24 kilograms, you get roughly 5 to 6 kilograms of lean mass gone. That is over 13 pounds of lean tissue, which includes muscle, connective tissue, and fluid, but a meaningful portion of it is contractile muscle.

The same 25 percent lean mass loss on a drug that only produces 10 kilograms of total weight loss would be 2.5 kilograms. The percentage is identical. The absolute loss is less than half. Retatrutide is not worse at protecting lean mass proportionally, but because the total weight loss is so much larger, the absolute number at the end is more significant than most people realize when they see "only 20 to 25 percent lean."

Now comes the piece of this data that challenges what the field expected.

Retatrutide is a triple agonist, meaning it activates three receptors instead of two or one: GLP-1, GIP, and the glucagon receptor. The glucagon component was theorized to be the feature that would make this drug different. Glucagon is a hormone your pancreas releases to raise blood sugar, but it also signals the liver to ramp up fat oxidation and increase energy expenditure. The hypothesis going into this drug was that activating the glucagon receptor would shift the body's fuel preference toward fat and spare lean tissue, producing a better ratio than you see with drugs that do not have that component.

What the DXA data shows is that the ratio is comparable to tirzepatide, which has no glucagon receptor at all.

There is a mechanism that may explain this. Research on glucagon receptor activation shows it also upregulates hepatic amino acid catabolism, meaning the liver breaks down amino acids more aggressively for energy when the glucagon signal is present. So the glucagon receptor may be doing two things at once: pushing fat oxidation up on one hand, and pushing amino acid breakdown up on the other, and those two effects may roughly cancel each other out in terms of the lean-to-fat loss ratio. The result is a drug that produces fat loss comparable in proportion to tirzepatide, but on a much larger absolute scale.

The practical implication of all this is straightforward.

If you are on retatrutide, the drug does not protect your lean mass for you. No GLP-1 class drug does, but this one matters more to get right because the total weight being moved is larger. The levers you have are resistance training and protein intake, and both have to be consistent to work.

Resistance training gives your muscle a reason to stay, because muscle is metabolically expensive and the body will not maintain tissue it is not using, so three to five sessions per week of compound, progressive loading sends the signal that the lean tissue should be preserved and the deficit should come from fat instead.

Protein intake matters because even when you are training, the body needs a sufficient supply of amino acids to rebuild and maintain muscle rather than pulling from it, and a general target of one gram per pound of goal body weight per day gives the liver enough substrate that it is not raiding your muscle to meet metabolic demand.

The drug creates the deficit that drives fat loss. Training and protein determine whether lean mass stays intact while that deficit runs.

The body composition percentage might look fine on the scan. The 13 pounds of lean tissue you lose if you skip the training says something different.

---

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.

---

Join the free community:
Men: Iron Forge Brotherhood
Women: Powerhouse Fitness