How comparable are tirzepatide and tirzepatide on the evidence available?

For reference: tirzepatide · tirzepatide.

I am trying to choose between two options that are usually discussed as though only one exists.

I am not optimising for price, but I am not indifferent to it either.

Which axes does this decision turn on?

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.

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.

SELECT reported a hazard ratio of 0.80 (95% CI 0.72–0.90) for the primary composite major adverse cardiovascular event endpoint with semaglutide 2.4 mg in overweight or obese adults with established cardiovascular disease and without diabetes[1].

The caveat is the population. Trial participants were screened, monitored and supported; the effect size in an unmonitored setting is not the trial effect size, and it is not obvious in which direction the difference runs.

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