New Insight on Muscle Loss with the Potency of Retatrutide

Retatrutide is that impressively potent obesity medicine that teased us with remarkable weight loss outcomes back in 2023. As we wait for pivotal phase three data (now due later this year), we wonder about the risk for muscle loss with a drug that has the potency of retatrutide.

A new paper in Lancet Diabetes & Endocrinology gives us reasons for both caution and reassurance. It tells us that yes, the concern about muscle loss is real and deserves attention with retatrutide. But no, it seems to be no worse with this medicine than it is with any other potent obesity treatment.

Most of the weight that people lose is fat mass. Body composition improves because of this. However, about 38% of the weight loss is from a loss of lean mass. And individual results will vary. So this deserves attention.

Evidence for Recommendations?

This insight leaves us wanting more research. Obviously, effects on body composition will be a focus when we see phase three results with retatrutide later this year. Absent any big surprises, though, the bigger question is what to do about it. The standard advice is to encourage patients to build a routine of strength training and a diet with adequate protein quantity and quality.

In a commentary on this new study, Carsten Dirksen and Sten Madsbad remind us of the need for more data to guide clinical recommendations. This is especially true for dietary counseling, they say:

“The recommended 0.8 g/kg per day of protein intake might be too little to provide protection of muscle mass and varying modes of protein intake; amino acid supplementation should be tested as part of weight loss programmes to mitigate loss of skeletal muscle.”

In new observational research presented at ENDO2025, Melanie Haines and colleagues found that adequate protein intake was predictive of less muscle loss in patients receiving semaglutide for obesity. Age and sex also appear to be important factors. Being older and female brings a higher risk of muscle loss.

So for now, we can lean upon expert opinion. Strength training and dietary counseling appear to help. For the future, we can hope for more robust evidence to guide expert recommendations.

Click here for the new study in Lancet Diabetes & Endocrinology, here for the commentary that comes with it. For the research abstract from Haines et al, click here and then here for further perspective.

Ecce Homo, painting by Titian / WikiArt

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July 18, 2025