SURMOUNT-4's randomised withdrawal design is the strongest available evidence about what happens on stopping. It says nothing about a lower maintenance dose, because the comparison was continue versus placebo rather than continue versus less.
Where I would look next, rather than where I would stop.
Offering a way to settle SURPASS-2 rather than another opinion about it. Two measurements, taken the same way, a fortnight apart. If the difference is within the noise, the question was not answerable at this precision.
On post #37 — agreed on the reasoning, with one qualification.
The practical version of SURPASS-2 is three sentences long. The rigorous version is three pages and reaches the same conclusion with the conditions attached.
SURMOUNT-4's randomised withdrawal design is the strongest available evidence about what happens on stopping. It says nothing about a lower maintenance dose, because the comparison was continue versus placebo rather than continue versus less.
SURMOUNT-4's randomised withdrawal design is the strongest available evidence about what happens on stopping. It says nothing about a lower maintenance dose, because the comparison was continue versus placebo rather than continue versus less.
On the mechanism question specifically: the honest position is that GIP agonism plausibly contributes and that the trial design cannot separate its contribution from simply achieving greater receptor engagement overall.
Answering the question post #91 raises rather than the one it answers.
Having read the whole SURPASS-2 thread before replying: the question in the first post has not actually been answered yet, and three of us have answered a nearby one instead.
Worth separating two things that post #100 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 quote the trial.
SURMOUNT-4's randomised withdrawal design is the strongest available evidence about what happens on stopping. It says nothing about a lower maintenance dose, because the comparison was continue versus placebo rather than continue versus less.
Same conclusion as the reply above, reached differently, which is mildly reassuring.
Read the full topic (112 posts)
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[2026 update] Does dual agonism explain the effect size, or is it dose?
Asking directly, because I could not find a straight answer: Does dual agonism explain the effect size, or is it dose? A question about dual agonism that I think has a definite answer, unlike most of what I…
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+58 | 63 | 40k | 9mo |
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SURPASS-2 and the comparator dose question that will not go away — what changed since
Posting this under the heading it deserves: SURPASS-2 and the comparator dose question that will not go away — what changed since Everything below is what sits behind that. What changes if the standard…
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+2 | 6 | 5.5k | 7h |
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The 2.5 mg starting dose is not a therapeutic dose — why that matters
The 2.5 mg starting dose is not a therapeutic dose — why that matters Writing it up because I had to work it out twice and would rather nobody else did. A follow-up question about 2.5 mg starting dose that I…
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+119 | 136 | 5.6k | 2mo |
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Follow-up: Tirzepatide and nausea: is the profile genuinely different or just differently reported?
Tirzepatide and nausea: is the profile genuinely different or just differently reported? I have a specific reason for asking rather than idle curiosity, and the context is below. Something about Tirzepatide…
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+109 | 122 | 3.6k | 2mo |
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Why tirzepatide titration schedules have more steps than semaglutide's
Asking directly, because I could not find a straight answer: Why tirzepatide titration schedules have more steps than semaglutide's I have spent a fortnight trying to pin tirzepatide titration schedules down…
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4 | 8.4k | 7mo |
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What SELECT changed about how semaglutide is discussed, and what it did not
Asking directly, because I could not find a straight answer: What SELECT changed about how semaglutide is discussed, and what it did not I was wrong about SELECT in a thread last spring and I would like to…
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+120 | 132 | 2k | 14mo |
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The "under review" status pill and when a moderator applies it — a second dataset
The "under review" status pill and when a moderator applies it — a second dataset Writing it up because I had to work it out twice and would rather nobody else did. A question about how this site should cite…
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+50 | 54 | 1.4k | 11mo |
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Selection into a registry and what it does to the estimate — a second dataset
Posting this under the heading it deserves: Selection into a registry and what it does to the estimate — a second dataset Everything below is what sits behind that. Posting a small dataset on Selection. It is…
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+28 | 32 | 1.3k | 1d |
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About the Progress reports category
Longitudinal self-reports with the method stated. Scales, tape measures, and their error bars. This post is a community wiki: any member at trust level 3 or above can edit it, and every edit is recorded with…
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4 | 139 | 16mo | |
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Primary endpoint hierarchies and why order matters — one year on
On the subject in the title: Primary endpoint hierarchies and why order matters — one year on Working notes rather than a conclusion. A follow-up question about Primary endpoint hierarchies that I did not…
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+56 | 61 | 37k | 11h |