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What fraction of loss on liraglutide is lean mass according to REDEFINE-1?

Asked 12 Mar 2025Modified 14 months agoViewed 28k times
20

The specifics, since they change the answer: liraglutide · REDEFINE-1.

I have the document in front of me and I can read the numbers. What I cannot do is interpret them.

I am reasonably comfortable with statistics and completely uncomfortable with chromatography, or vice versa.

Which parts of this are informative and which are decoration?

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LM
askedlucia_marchetti18k2812 Mar 2025
6Note that the label instructions differ between agents on precisely this point. – bufferline42 3 months ago
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5 Answers

Accepted answer first, then by votes
39

Accepted answer

Mechanically, 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.

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.

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].

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.

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

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DV
answered · acceptedDr_Ilse_Vandenberg78k24812 May 2025
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15

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.

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.

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

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.

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

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PC
answeredpierce_count15k281 May 2025
3Note that the label instructions differ between agents on precisely this point. – carys_meredith 36 days ago
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13

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

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.

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.

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.

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.

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

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DA
answeredDr_Yusuf_Adeyemi95k2489 Apr 2025
6The arithmetic checks out. I ran the same numbers and got the same result. – halvard_ness 5 days ago
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To be exact about it, the mechanism is worth having straight, because it predicts which interventions can work and which cannot.

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

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IB
answeredines_brandt93k24820 Apr 2025
Confirming from the other direction: I did the wrong thing and got exactly the predicted outcome. – cake_intact 3 months ago
8Is there a reason to prefer the second method over the first, other than cost? – sian_llewellyn 2 months ago
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-3

Put another way, 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.

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.

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.

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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EV
answeredesther_vandeVelde49k3823 May 2025

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