[2026 update] What the GIP component of tirzepatide is thought to contribute, and how confident we can be posts 121–125

Tirzepatide's half-life of roughly five days means steady state is approached in about three weeks rather than four. That is a real difference from semaglutide and it is small enough that the weekly schedule is unaffected.

The literature is thinner on this than the confidence in the thread implies.

The five maintenance doses in the tirzepatide programme give a genuine dose-response curve, which is unusual. Most trials in this space compare one or two doses against placebo and cannot say anything about the shape of the relationship.

I would rather be precise about what I do not know than vague about what I do.

Categorical response thresholds — the proportion reaching ten, fifteen or twenty per cent reduction — are more persuasive and less informative than the mean. They depend entirely on where the threshold was drawn.

Post #122 describes the usual case. This is about the unusual one.

Mass and charge states: tirzepatide is about 4813.5 Da and on an electrospray instrument you would expect to see charge states mostly in the 2+ to 4+ range, the same as semaglutide. A doubly charged species would appear at about (4813.5 + 2 × 1.008) / 2 ≈ 2408.

Post #124 is right about the mechanism and I think understates the practical bit.

Agreed on GIP component of tirzepatide, with one qualification that I think matters. The reasoning holds for the case as described. Change the starting assumption and it does not, and the starting assumption is the part nobody states.