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Why do two papers on SUSTAIN-6 report different headline figures?

Asked 21 Jun 2026Modified 21 days agoViewed 2k times
9

I have three data points across nine months, which I hope is enough to see a trend.

I suspect the usual explanation for this is wrong, or at least incomplete.

I am aware this may have a boring answer. I would still like the boring answer stated clearly.

Can someone derive this rather than assert it?

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askedsamir_bennani13k1821 Jun 2026

1 Answer

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Specifically, read the estimand before the effect size. Almost every apparent contradiction between two published figures from the same trial resolves once you notice that one is a trial-product estimand and the other is a treatment-policy estimand.

Absolute risk reduction, worked: if the control-arm event rate is 8.0 per cent over the follow-up period and the hazard ratio is 0.80, the treated rate is approximately 6.4 per cent, the absolute risk reduction is 1.6 percentage points, and the number needed to treat is 1 ÷ 0.016 ≈ 63 over that period. A 20 per cent relative reduction and a number needed to treat of 63 are the same finding stated two ways, and only one of them sounds impressive.

The part that matters: creatinine is a muscle-derived metabolite, so a substantial loss of lean mass lowers serum creatinine and mathematically raises estimated GFR without anything happening to the kidney. If you have lost twenty kilograms, your creatinine-based eGFR is flattering you. Cystatin C is not muscle-dependent and is the measure to use when the two disagree.

SURMOUNT-4 randomised participants after an open-label lead-in to continued tirzepatide or placebo, and the withdrawal arm regained a substantial proportion of the lost weight over the following year[1].

Worth being explicit that this is interpretation of published data and not medical advice. Laboratory results belong in a conversation with whoever ordered them.

Read the confidence interval, read the estimand, and compute the absolute effect yourself. It takes two minutes and it changes how the result feels.

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answeredtobias_maartens94k2589 Jul 2026
2The timing signature is the useful part. Everything else is confounded. – rae_oyelowo 7 months ago
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