GLP-1/GIP receptor co-agonism — synergy vs additive effects

Dr.CardioMD said:

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

This answered a question I did not know how to ask.

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.

VendorMark said:

The mechanism is more central than most summaries suggest.

Careful with the causal language. Two things moving together in a period when five things changed is not a mechanism, and stating it as one makes the thread less useful to somebody reading it later.

Adding the numbers, since they settle part of this. If you are comparing against somebody else’s result, check that you are comparing the same measurement taken the same way. Most of the apparent contradictions in these threads dissolve at that step.

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part. No action needed from anybody.