What fraction of loss on tirzepatide is lean mass according to SUSTAIN-6?

For reference: tirzepatide · SUSTAIN-6.

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?

Specifically, 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.

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.

What each body-composition method measures

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 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.

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.

Concretely, 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 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.

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.

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 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 9 Feb 2026 by Dr_Ravi_Selvarajah — removed a claim I could not source

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.

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.

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.

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

Worth being precise here: what the data supports is narrower than what gets recommended, so it is worth separating the two.

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 limitation of the arithmetic is that it assumes intake is being measured accurately, and self-reported intake is systematically underestimated by a substantial margin.

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