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What fraction of loss on dulaglutide is lean mass according to TRIUMPH-1?

Asked 14 Jul 2024Modified 20 months agoViewed 14k times
11

What I am working with: dulaglutide · TRIUMPH-1.

I have read the primary source rather than the summary, which has left me with more questions.

I understand the headline. I do not understand the footnotes, and the footnotes look important.

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

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askedshear_at_the_front15k2814 Jul 2024

5 Answers

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

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.

Specifically, 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.

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.

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

edited 22 Nov 2024 by v_ramaswamy — expanded the table to cover the lower concentration

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VR
answeredv_ramaswamy40k3810 Nov 2024
3Two of us worked through this independently and arrived here, so it is at least reproducible. – e_dziedzic 5 months ago
2Worth adding that the method section is where the answer usually is. – Dr_Jonas_Halvorsen 4 months ago
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41

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 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 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.

edited 25 Jul 2024 by orla_ferriter — removed a claim I could not source

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OF
answeredorla_ferriter47k3825 Jul 2024
34

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

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.

The underlying point is that 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 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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DZ
answeredDr_Marek_Zielinski39k385 Aug 2024
24

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

The regain trajectory after stopping is roughly a mirror of the loss trajectory, and it is not primarily a willpower phenomenon. Appetite signalling returns, energy expenditure remains suppressed relative to the original mass, and the two combine. That is an argument for a maintenance plan existing before the stop, rather than an argument against stopping.

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].

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

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DF
answeredDr_Colm_Fitzhenry85k24827 Sept 2024
-3

On the detail: 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.

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 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].

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

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KA
answeredkwn_analytical89k24816 Aug 2024

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