The case in front of me: semaglutide · SUSTAIN-6.
I would like to know the limits of what can be inferred from this.
What I am trying to avoid is over-reading a single result, which I have done before.
What can I legitimately conclude from this figure?
Take the SUSTAIN-6 body-composition substudy, not the main paper, and note how few participants were in it. Composition substudies are typically a small imaged subset of the full randomisation, so the lean-mass fraction carries a confidence interval far wider than the weight figures beside it. Then check the method: DEXA reports lean soft tissue, which includes water, and a large early fluid shift is counted as lean loss whether or not any protein left. The fraction most of these programmes land near is around a quarter of total loss, which is also roughly what caloric restriction alone produces — the interesting question is not the fraction but whether it differs from the deficit-matched control.
To be exact about it, preserving lean mass and gaining it are different objectives with different requirements, and in an energy deficit only the first is realistic for most people.
Because appetite is suppressed in this class, protein intake tends to fall in absolute terms even when it rises as a percentage of a smaller intake. That is the specific mechanism by which lean loss gets worse here.
Bone mineral density is measured on the same scan and falls slowly with weight loss; it is worth tracking on the same series rather than as a separate exercise.
Trials in this class that measured body composition report lean fractions broadly consistent with other weight-loss interventions of similar magnitude.
Nothing here is medical or dietetic advice, and anyone with kidney disease has a protein question that needs a clinician.
Do not read the first fortnight as tissue loss. It is mostly glycogen and its water.
edited 7 Apr 2025 by Dr_Wren_Halliday — added a caveat about sampling
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsAnswer first: lean mass falls during any substantial weight loss, typically as twenty to thirty per cent of the total, and the levers that change that fraction are protein intake and resistance training rather than anything pharmacological.
Glycogen depletion in the first fortnight releases the water bound to it — roughly three grams of water per gram of glycogen — which shows up as several kilograms of "lean mass" lost before any tissue has gone anywhere.
The conventional figure is that lean tissue accounts for roughly a quarter of total weight lost in unstructured weight loss, falling towards ten to fifteen per cent with adequate protein and progressive resistance training, and rising above a third with very rapid loss and no training stimulus.
Comparing scans from different machines is not a comparison. Different manufacturers use different algorithms.
Protein and progressive resistance training. Those are the two levers; everything else is a detail.
Start with what "lean mass" means on your report, because it is fat-free mass including water, glycogen and organ tissue — not muscle protein.
Scan-to-scan precision on lean mass is around one to two per cent for a good DXA under standardised conditions, so a change of half a kilogram is inside the noise.
A daily protein intake in the range of 1.6 to 2.4 grams per kilogram of reference body weight is the range the resistance-training literature supports for lean-mass preservation in a deficit. At the top of that range the marginal return is small.
Track absolute lean mass, not lean percentage, or the arithmetic will mislead you.
Absolute lean mass and lean mass as a percentage move in opposite directions during fat loss, which causes endless confusion.
Resistance training two to four times weekly with progressive load is the intervention with the strongest evidence for reducing the lean fraction of loss. Cardiovascular exercise does not substitute for it on this endpoint.
Same machine, same time of day, same hydration state, or the series is noise.
Answering this needs the rate of loss, because faster loss reliably costs a larger lean fraction.
A deficit of five hundred to seven hundred and fifty kilocalories per day is the range within which lean preservation is generally achievable. Larger deficits work faster and cost more lean tissue per kilogram lost.
Research-use compounds are not approved for human use, and body-composition planning does not change that.
A quarter is typical. Below a fifth is a good outcome. Above a third means slow down.
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.