Muscle Volume Versus Muscle Function on a GLP-1

The standard worry about GLP-1 drugs is that they take muscle along with fat, and it is a real effect that shows up in every body-composition study. A 2025 analysis measured both halves of the question in the same people and found something the alarming version leaves out: psoas muscle volume fell 9.3% over 24 weeks, while chair-rise time and walking speed both moved slightly better.^[1]

Mass and function are different measurements

This is the distinction the whole debate turns on, and it is usually collapsed. Muscle mass is what a scan measures. Muscle function is whether you can stand up from a chair and walk across a room. They are correlated, they are not the same, and only one of them is what anybody actually wants.

In this study, participants received semaglutide for 24 weeks, titrated to 1 mg a week. Psoas muscle volume was measured on MRI and fell by 9.3%, a highly significant change. Physical function was assessed by a ten-time chair rise and a four-meter gait speed test. Chair rise improved by 1.27 seconds and gait speed by 0.05 meters per second — neither statistically significant, but both pointing the opposite way from the scan.^[1]

Why the muscle loss is expected, not alarming on its own

Losing weight of any kind costs lean tissue. It happens with dieting, with bariatric surgery and with illness, and it happens because a smaller body needs less muscle to move itself. The question that matters is not whether lean mass falls — it always does — but whether the person ends up weaker.

On that question, this study is reassuring and thin. Our article on what the trials measured covers the body-composition side in the larger programs, and the practical response — resistance training and adequate protein — has not changed and is not controversial.

The comparison that answers the question best

A larger MRI study went further, and it did the one thing that turns muscle numbers into an answer: it compared them against what would be expected anyway. SURPASS-3’s imaging substudy scanned 246 people with type 2 diabetes at baseline and week 52, randomized to tirzepatide at three doses or to titrated insulin, and then set the results against longitudinal MRI data from UK Biobank participants.^[2]

Read alone, that is the alarming version: muscle volume down, and down relative to what body size would predict. All three changes reached p<0.0001 and all three differed significantly from the insulin arm, where body weight and muscle volume both rose modestly.

So the muscle that went was about what you would expect to go. The muscle that stayed was less infiltrated with fat than expected — which is a measure of muscle quality, and it moved in the favorable direction beyond what the weight loss alone would account for.

The insulin arm makes the same point from the other side. Those participants gained weight and gained muscle volume, and their muscle fat infiltration did not significantly improve. More muscle, no better quality. Volume on its own is not the thing to want.

Two limits. This was a post-hoc exploratory analysis in people with type 2 diabetes and fatty liver, not a general population. And a UK Biobank comparison is a modeled expectation rather than a matched control group — a good one, and not the same as randomizing people to lose weight another way.

How much weight this can carry

Not much, and it is worth being blunt about why. This was a single-arm study — there was no control group. Everyone received the drug, so a functional improvement cannot be attributed to it. People who enroll in a study, lose weight and get tested twice may walk faster for reasons that have nothing to do with semaglutide.

• 51 participants, with muscle measures in 46. Small enough that the non-significant functional results may simply be underpowered rather than genuinely flat.
• 24 weeks, and titrated only to 1 mg a week — below the 2.4 mg used for weight management. Both the duration and the dose are modest.
• A specific population: people with HIV and metabolic dysfunction-associated steatotic liver disease, with a mean age of 50 and a mean BMI of 35.5.
• A secondary analysis. The parent study, SLIM LIVER, was designed to ask about liver fat. Muscle was not its primary question.

A single-arm study cannot tell you what a drug did. It can tell you what happened, which is sometimes enough to correct a bad assumption.

And that is the honest value here. It does not prove GLP-1 drugs preserve function. It does show that a substantial fall in measured muscle volume can happen alongside stable or slightly improved physical performance — which means a scan showing lost lean mass is not, by itself, evidence that someone has been harmed.