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

Asked 28 Apr 2025Modified 13 months agoViewed 18k times
30

Stated plainly: dulaglutide · STEP 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 can I legitimately conclude from this figure?

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DC
askeddrawn_and_capped15k2828 Apr 2025
7For what it is worth, my own result was within half a per cent of this. – sian_llewellyn 10 months ago
8Any reason this would differ for a longer peptide? – cake_intact 2 months ago
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4 Answers

Accepted answer first, then by votes
76

Accepted answer

To be exact about it, 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.

It helps to be literal here: 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.

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].

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.

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

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DB
answered · acceptedDr_Aoife_Brennan50k4826 May 2025
The arithmetic checks out. I ran the same numbers and got the same result. – m_haraldsen 5 months ago
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67

The underlying point is that 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.

To be exact about it, 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.

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.

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

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JV
answeredjo_vandeberg19k2714 May 2025
35

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.

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].

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

edited 10 Jun 2025 by rota_site — added the method parameters

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RS
answeredrota_site55k386 Jun 2025
8This is the answer I was looking for three months ago. – marta_okonkwo 16 days ago
The arithmetic checks out. I ran the same numbers and got the same result. – tenth_of_a_unit 2 months ago
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28

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 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.

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

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LC
answeredlyoph_cake95k25817 Jun 2025
3The placebo-arm figure is the part everyone omits. – coldpack_88 7 months ago
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