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What fraction of loss on semaglutide is lean mass according to SURMOUNT-2?

Asked 29 Mar 2025Modified 15 months agoViewed 13k times
2

Concretely: semaglutide · SURMOUNT-2.

The figures are clear enough; the question is what they mean and what they do not.

I can supply the numbers if the specifics change the answer.

What would I need in addition before this supported a decision?

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RP
askedravenna_pace13k2729 Mar 2025
4Have you seen anything published on this, or is it inference from the mechanism? – Dr_Rosalind_Achebe 9 months ago
3Useful. I have added the accept threshold suggestion to my own notes. – micron22 8 months ago
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4 Answers

Accepted answer first, then by votes
44

Accepted answer

The relevant detail is that the distinction that resolves this is between proportional loss and functional loss. Losing lean mass in proportion to total mass is what happens in every weight loss intervention. Losing function is not, and function is measurable.

Fibre at very low total intake is a trap. Soluble fibre needs water and motility to work; insoluble fibre adds bulk to a slow transit. At 900 kcal a day with delayed gastric emptying, an osmotic agent is more predictable than a bulking one, and adequate fluid is doing more work than either.

The minimum effective resistance-training dose in a deficit is lower than most programmes assume. Two sessions a week covering the major movement patterns, with loads taken close to failure, is sufficient to retain most of what would otherwise be lost. Volume beyond that adds recovery cost that a large energy deficit is poorly placed to pay.

The evidence for a higher protein intake preserving lean mass during an energy deficit is reasonably strong in resistance-trained populations and weaker in sedentary ones, with the meta-analytic estimates supporting intakes in the region of 1.6 g/kg over lower intakes when training is present[1].

The plateau is arithmetic. Treat it as arithmetic and the response follows.

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IB
answered · acceptedines_brandt93k2489 May 2025
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39

The underlying point is that the mechanism is worth having straight, because it predicts which interventions can work and which cannot.

Absolute strength holds up better than scale weight during a deficit for a straightforward reason: strength is substantially neural and skill-based, and the contractile tissue you retain is being trained harder relative to its size. Grip strength and repetition maxima are therefore lagging indicators of muscle loss rather than leading ones, which is an argument for measuring both.

Cardio does not interfere with lean-mass retention at the volumes anyone here is doing; the interference effect in the literature appears at high concurrent volumes in trained athletes. What cardio does at a large deficit is add to the deficit, which is either the point or a problem depending on the objective.

One qualification: none of this is a clinical assessment, and unexplained loss of function rather than of mass is a reason to see someone rather than to adjust a programme.

Train, eat the protein, measure something functional, and give the trend three months before you interpret it.

edited 11 May 2025 by esther_vandeVelde — fixed an arithmetic slip in the third paragraph

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EV
answeredesther_vandeVelde49k3828 Apr 2025
3Small correction: the units in the third paragraph should be micrograms, not milligrams. – sian_llewellyn 39 days ago
4Do you have a reference for the last claim? Not disputing it, just want to read it. – cake_intact 3 months ago
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18

The relevant detail is that what the data supports is narrower than what gets recommended, so it is worth separating the two.

Hydration state moves a DEXA lean-mass figure directly, because the algorithm assigns water to the lean compartment. Scanning fasted, at the same time of day, before training and without a recent high-carbohydrate day is the difference between a comparable sequence and a noisy one. Bioelectrical impedance is far more sensitive to hydration again, which is why its trend is unusable at this timescale.

Mechanically, food noise returning is not obviously tolerance. Receptor desensitisation is one hypothesis; a second is that the initial effect was partly novelty and partly the steep early deficit, and a third is that intake has drifted upward and the signal is being outcompeted rather than weakened. The three make different predictions about what a dose increase would do.

Worth stating that a DEXA sequence is only as good as its protocol consistency, and most people’s sequences are not consistent enough to support the conclusions drawn from them.

Measure strength as well as mass. It is cheaper, it is less noisy, and it is closer to what you actually care about.

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HP
answeredhana_petrikova19k286 Apr 2025
14

The underlying point is that a plateau at four to six months is the expected shape of the curve, not a failure of it. Energy expenditure falls with mass, and the deficit closes itself unless intake falls further.

DEXA precision is better than people assume for fat mass and worse than people assume for lean mass in a single scan — the least significant change for regional lean mass on a well-maintained scanner is on the order of a few per cent. That means two scans three months apart can differ without anything having happened, and it means a scan sequence needs to be at least three points before a trend is interpretable.

The STEP 1 extension reported substantial regain in the year after treatment withdrawal, with weight and cardiometabolic variables trending back toward baseline[1].

Two resistance sessions a week and a protein target you actually hit will do more than any refinement beyond them.

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RP
answeredrhian_prydderch44k3817 Apr 2025
The timing signature is the useful part. Everything else is confounded. – RP_C18 5 months ago
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