SURPASS-CVOT: tirzepatide cardiovascular outcomes trial design — need advice

sarah_TO said:

The GIP arm is doing real work rather than padding the label.

That reframing is the part I needed.

Clinical perspective, offered as context rather than as advice.

Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows:

Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill coefficient ≈ 1.3
Tirzepatide: ED50 ≈ 6mg, Emax ≈ -25%, Hill coefficient ≈ 1.5

Clinical implication: most patients achieve >80% of maximal response by the mid-range dose (1.7mg sema, 10mg tirz). Going to the maximum dose provides diminishing returns — possibly not worth the additional side effect burden for some patients. Individualize dosing based on response vs tolerability.

Dr.Martinez said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

I read this differently from Dr.Martinez, on substance rather than tone. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

One concrete data point for the thread. One habit that pays for itself: post the method alongside the number. A figure without its method cannot be checked, and an unchecked figure is how this community accumulates folklore.

Correct me if the detail matters more than I have assumed.

Moderator note: two posts asking for a source have been merged into one. Please search the thread before asking again. Thread quality here is what the rules are for. Keep it up.