Dual agonism versus dose: how much of tirzepatide's effect is the GIP component and how much is simply achieving higher receptor engagement? The honest answer is that the question is not settled. Some of the effect is surely the GIP component, but the trial design does not decompose it.
Topic summary
The 2.5 mg starting dose is not a therapeutic dose — why that matters
This is a generated summary. It shows the 9 most-liked posts from a topic of 137, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.
I read post #16 twice before replying, because I had assumed the opposite.
Two things before anyone answers the substance.
First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.
30 likes 5mo
On post #21 — agreed on the reasoning, with one qualification.
Two things before anyone answers the substance.
First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.
30 likes 5mo
ma.balogun, post #30: post #29 is right about the mechanism and I think understates the practical bit. SURMOUNT-1 reported weight reduction of a magnitude that was the largest for a pharmacological intervention at that time of publication. It also reported a clear dose response across three doses. The categorical thresholds (people reaching 10%, 15%, 20%… Go to post
Coming back to post #34, because the follow-up matters more than the original answer.
SURMOUNT-4 used a randomised withdrawal design: everyone titrated, then those on maintenance were randomised to continue or placebo. Continuation maintained effect; withdrawal was followed by regain. The finding is robust but it says nothing about a lower effective maintenance dose, because that was not studied.
Worth separating two things that post #56 runs together.
The 2.5 mg starting dose is not a therapeutic dose in the sense that weight loss is minimal at that dose. It is a tolerance-testing dose. Confusing the purpose of a starting dose with the purpose of a maintenance dose leads to false conclusions about efficacy.
29 likes 4mo
This follows post #87 rather than contradicting it.
Storage and stability: published data on licensed tirzepatide formulations exists and is worth reading directly rather than through summarised claims. Reconstituted preparations in different diluents have not been studied and extrapolation from the licensed formulation is the best you can do.
29 likes 3mo
v.salgado, post #76: I read post #74 twice before replying, because I had assumed the opposite. Dual agonism versus dose: how much of tirzepatide's effect is the GIP component and how much is simply achieving higher receptor engagement? The honest answer is that the question is not settled. Some of the effect is surely the GIP component, but the trial… Go to post
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
ra.mensa, post #2: Nausea profile: some people report tirzepatide as less nausea-prone than semaglutide, others report it as more. The trial reported gastrointestinal effects broadly comparable in character. Individual variation is the largest factor. Go to post
Storage and stability: published data on licensed tirzepatide formulations exists and is worth reading directly rather than through summarised claims. Reconstituted preparations in different diluents have not been studied and extrapolation from the licensed formulation is the best you can do.
k.salinas, post #9: Worth separating two things that post #5 runs together. SURPASS-2 compared tirzepatide with semaglutide 1.0 mg, the licensed diabetes dose at that time. It did not compare with semaglutide 2.4 mg, the highest approved dose. That is the central and legitimate criticism of the head-to-head evidence and it is worth remembering when people… Go to post
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
Read the full topic (137 posts)
This topic was referenced in
- Revisiting: Why tirzepatide titration schedules have more steps than semaglutide'sCompounds › Tirzepatide · 101 replies
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