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What fraction of loss on dulaglutide is lean mass according to SURPASS-2?

Asked 3 Feb 2025Modified 15 months agoViewed 29k times
24

Stated plainly: dulaglutide · SURPASS-2.

I would like help reading this properly rather than being told what conclusion to reach.

I have the full report including the method section, so I can quote specifics if that helps.

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

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TW
askedtamsin_wray13k173 Feb 2025
7Confirming from the other direction: I did the wrong thing and got exactly the predicted outcome. – unit_math 3 months ago
8Is there a reason to prefer the second method over the first, other than cost? – micron22 5 months ago
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5 Answers

Accepted answer first, then by votes
76

Accepted answer

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.

Protein target arithmetic

Body mass1.2 g/kg1.6 g/kg2.0 g/kgPer meal at 1.6 (÷3)
62 kg74 g99 g124 g33 g
74 kg89 g118 g148 g39 g
88 kg106 g141 g176 g47 g
103 kg124 g165 g206 g55 g
124 kg149 g198 g248 g66 g

At roughly 4 kcal per gram, 141 g of protein is about 564 kcal — a substantial fraction of a 900 kcal budget, which is the real constraint.

Concretely, 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.

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].

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

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IB
answered · acceptedines_brandt93k2481 Apr 2025
8I tested this on two lots and got the same answer, so at least it reproduces. – lyoph_cake 7 months ago
The timing signature is the useful part. Everything else is confounded. – syringe_ninety 9 months ago
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85

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.

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.

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

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.

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

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LS
answeredlow_dead_space42k3810 Mar 2025
56

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

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.

Specifically, 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.

The caveat is that population averages tell you about populations. Your own trajectory is a sample of one and should be read as a trend, not as a deviation from a published mean.

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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DF
answeredDr_Nadia_Farsi90k25821 Mar 2025
Related: the same reasoning applies to the counter-ion question. – Dr_Tomas_Kral 2 months ago
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35

What the data supports is narrower than what gets recommended, so it is worth separating the two.

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.

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.

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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FU
answeredforty_units14k1713 Apr 2025
27

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 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.

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.

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

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CC
answeredcake_collapsed13k2824 Apr 2025

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