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What fraction of loss on ecnoglutide is lean mass according to SURPASS-3?

Asked 24 Jul 2024Modified 22 months agoViewed 35k times
34

Concretely: ecnoglutide · SURPASS-3.

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 can I legitimately conclude from this figure?

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askedayo_fadipe19k2824 Jul 2024

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

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.

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.

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.

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].

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

edited 8 Oct 2024 by sunniva_dahl — added the method parameters

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SD
answeredsunniva_dahl11k289 Sept 2024
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39

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.

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.

Stated carefully, 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.

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.

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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AB
answeredassay_blank39k3820 Sept 2024
29

In practice, 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.

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.

It helps to be literal here: 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].

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.

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

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SL
answeredsian_llewellyn85k24818 Aug 2024
4I have seen exactly this failure mode twice and both times it was the diluent. – halvard_ness 8 months ago
5The distinction between purity and content cannot be repeated often enough here. – tandem_gradient 9 months ago
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23

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.

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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DS
answeredDr_Ravi_Selvarajah42k13827 Jul 2024
22

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.

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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CI
answeredcake_intact18k2829 Aug 2024
The distinction between purity and content cannot be repeated often enough here. – eighty_six_hours 2 months ago
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