Obesity drugs strip muscle along with fat. The fix that made headlines this week is a monthly antibody infusion. A mouse study published the next day says a cheap ketone drink did much the same thing.
The headline fix came in Nature Medicine on June 8. Researchers gave 102 people with overweight or obesity weekly tirzepatide, the drug sold as Mounjaro, for 24 weeks, and gave half of them a monthly infusion of apitegromab, an experimental antibody that blocks myostatin, the body's brake on muscle growth. The antibody group lost about half as much lean mass as the people on tirzepatide alone, and scored slightly better on grip and leg-strength tests. The Guardian ↗ and the BBC ↗ both ran it, the BBC under the headline "Ozempic butt."
How much of the weight people lose on these drugs is muscle rather than fat is itself unsettled. The BBC put it at a third. The Nature Medicine team and several others land at 25 to 40 percent. The new mouse paper cites a figure as high as 45 percent. Lean mass is not all muscle, it also counts organ tissue and blood, but the muscle share is the part that matters for staying strong and mobile, and the spread between a third and nearly half is wide enough that the honest answer is nobody has pinned it down.
The second fix is a drink. In JCI Insight ↗, a team led by Yasser Abuetabh at the University of Alberta put obese, glucose-intolerant mice on one of three regimens for three weeks: a placebo, semaglutide alone, or semaglutide plus an oral ketone ester, a supplement that floods the blood with beta-hydroxybutyrate, the same fuel the body makes during fasting. Semaglutide on its own did what it does in people. It cut lean mass, weakened the animals' muscles, dialed down the genes that run muscle mitochondria, and switched on the genes that drive muscle wasting. Adding the ketone ester held the line. The mice kept their muscle mass and their strength, and they lost just as much fat as the semaglutide-only group.
That last point is the one that matters. A muscle-preserving add-on is only useful if it does not blunt the weight loss people took the drug for, and the ketone ester did not. Mechanistically the two fixes work from opposite ends. Apitegromab blocks a signal to build muscle back. The ketone ester appears to keep the existing muscle running, by protecting the mitochondria and the metabolic machinery that semaglutide knocks down.
The muscle-loss problem now has a small pile of competing answers, and peptidemodel has been tracking them. A glucagon-leaning co-agonist preserved lean mass in one earlier readout. Then came an aging-enzyme block that restored muscle ↗ trimmed by semaglutide. Now a ketone ester. One is a redesigned drug, one is an injectable biologic, one is a supplement already sold to endurance athletes. They are not interchangeable, but they are aimed at the same target, and the cheapest of them just posted positive preclinical data.
The caveats on the ketone study are the usual ones, and they are real. This is three weeks in mice, with the strongest evidence coming from gene-expression readouts rather than long-term outcomes, and ketone esters are expensive per dose and famously unpleasant to drink. None of that has been tested against semaglutide ↗ in a person. But the case for treating GLP-1 ↗ muscle loss as a solvable engineering problem, rather than an unavoidable tax on weight loss, keeps getting stronger, and it no longer all runs through myostatin ↗.