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Is SURMOUNT-4 a fair comparison of orforglipron against its comparator arm?

Asked 25 Nov 2025Modified 8 months agoViewed 17k times
29

Details up front: SURMOUNT-4 · orforglipron.

I would rather be corrected now than propagate something wrong.

I am specifically not interested in a testimonial; I am interested in a measurement.

What would count as evidence here, and does it exist?

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askedhana_petrikova19k2825 Nov 2025

1 Answer

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It helps to be literal here: start with the population. The inclusion criteria of the trial determine what its result can be extrapolated to, and the extrapolation people want is usually to a population the trial excluded.

Estimated average glucose from HbA1c: eAG in mg/dL = 28.7 × A1c − 46.7, or in mmol/L, 1.59 × A1c − 2.59. An A1c of 6.5 per cent is therefore about 140 mg/dL or 7.8 mmol/L. The relationship is a population regression, so an individual can sit well off the line.

Relative to absolute, worked

QuantityValueDerivation
Control-arm event rate8.0 %From the trial table, not the abstract
Hazard ratio0.80Reported
Treated event rate6.4 %8.0 × 0.80
Absolute risk reduction1.6 pp8.0 − 6.4
Number needed to treat631 ÷ 0.016
Relative risk reduction20 %1 − 0.80

The last two rows describe the same finding. Only one of them is used in headlines.

The part that matters: hbA1c is a weighted average, not a flat one: roughly half the signal comes from the most recent month. That is why a value drawn six weeks after a change already reflects most of the effect, and why a value drawn during rapid haematological turnover reflects something other than glycaemia.

The papers are readable. Read the paper rather than the summary of the paper, especially where the summary is enthusiastic.

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answerednine_point_nine45k1387 Dec 2025
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