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What fraction of loss on mazdutide is lean mass according to STEP 3?

Asked 4 May 2026Modified 7 days agoViewed 7.8k times
11

Numbers first: mazdutide · STEP 3.

This is presented as though it settles something, and I am not convinced it does.

I have two documents that appear to disagree, which is what prompted this.

Which parts of this are informative and which are decoration?

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askedt_oyelaran41k384 May 2026
2The placebo-arm figure is the part everyone omits. – teodora_ilic 5 months ago
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5 Answers

Accepted answer first, then by votes
20

Accepted answer

The commonly quoted figures for lean-mass loss are mostly measurement artefacts, and the artefact is well understood: fat-free mass as measured includes water and glycogen, both of which fall early and neither of which is contractile tissue.

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 first four weeks of loss is substantially fluid and glycogen. Each gram of stored glycogen carries roughly three grams of water, and total glycogen is on the order of 400 to 500 g, so the obligatory water shift alone accounts for a couple of kilograms. This is why the first month looks dramatic and the second looks like a plateau when in fact the fat-loss rate has not changed.

SURMOUNT-4 provides the cleanest maintenance-versus-withdrawal contrast available in the class, and it is the reference for any claim about what happens after stopping[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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answered · acceptedhalvard_ness42k3824 May 2026
5Worth flagging that this changed in 2025, so older answers on the site are out of date. – low_dead_space 8 months ago
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7

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.

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.

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.

The limitation of the arithmetic is that it assumes intake is being measured accurately, and self-reported intake is systematically underestimated by a substantial margin.

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

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answeredmira_sundqvist19k1831 May 2026
8Does this hold at lower concentrations, or does adsorption dominate? – sian_llewellyn 34 days ago
Worth flagging that this changed in 2025, so older answers on the site are out of date. – pk_curve 3 months ago
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6

Start with the arithmetic, because the answer to the practical question is usually a number and the number is usually achievable.

Protein target, worked: at 88 kg, a target of 1.6 g/kg is 88 × 1.6 = 141 g per day. Spread across three eating occasions that is roughly 47 g each, and the leucine threshold for a maximal muscle protein synthetic response is met at around 2.5 to 3 g of leucine, which corresponds to roughly 30 to 40 g of a high-quality protein. So three meals at 40 g plus one 25 g snack gets you to 145 g and clears the per-meal threshold each time. On 900 kcal that leaves about 340 kcal for everything else, which is the actual constraint.

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.

Adaptive thermogenesis — a fall in energy expenditure beyond that predicted by the change in body composition — is documented across weight-loss interventions and is the mechanistic basis for the plateau being expected rather than anomalous.

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

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answeredDr_Bram_Verhoeven85k24810 May 2026
5

To be exact about it, what the data supports is narrower than what gets recommended, so it is worth separating the two.

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.

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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answeredDr_Elias_Weiss46k3817 May 2026
I tested this on two lots and got the same answer, so at least it reproduces. – Dr_Tomas_Kral 6 months ago
2The arithmetic checks out. I ran the same numbers and got the same result. – Dr_Ilse_Vandenberg 7 months ago
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2

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

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 body-composition substudies in the major programmes consistently report that the proportion of weight lost as fat mass is approximately three quarters or better, with the lean-mass fraction falling within the range seen in dietary weight loss of comparable magnitude[1].

I would be careful with the supplement literature here; effect sizes are small, the studies are mostly in trained young men, and generalisation to a large deficit is not obviously valid.

A maintenance plan written before you need it is worth more than a better loss plan.

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answeredDr_Ilse_Vandenberg78k24823 Jul 2026

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