What the published dose-response for semaglutide actually looks like above 2.4 mg — a second dataset posts 121–131

Answering the question post #117 raises rather than the one it answers.

Semaglutide versus liraglutide in STEP 8: semaglutide produced greater weight reduction and the discontinuation rates differed. But the trial was open-label for the dosing schedule, which admits expectation effects. Weekly versus daily itself is part of the comparison, not a confounding variable to be removed.

Adding the boring version of published dose-response for semaglutide, because the interesting version keeps getting posted and the boring one is usually right.

Check the ordinary explanations, in order, and stop when one of them accounts for what you are seeing. Most of the time the second one does.

The confident answers on published dose-response for semaglutide and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.

Building on post #121 rather than restating it.

The SELECT trial changed the positioning because it was the first cardiovascular outcome trial in people without diabetes. That decoupled the cardiovascular argument from glycaemic control, which is why it mattered beyond its own numbers.

On the injection-day question: the labelling for licensed semaglutide allows the day to be changed provided at least two days separate the two injections. That interval is not arbitrary — it is what stops two doses stacking inside one absorption window.

I would treat the number as indicative rather than as a measurement.

The C-cell question: semaglutide triggered medullary thyroid carcinoma in rodent toxicology studies. A signal in rodents does not automatically appear in humans, but it is the reason the compound is contraindicated in people with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.

One of those cases where knowing the mechanism does not help the decision.

Where I part company with post #125, and it is a narrow parting.

Worth separating published dose-response for semaglutide as a question about the compound from published dose-response for semaglutide as a question about the documentation. They get answered by different people and only one of them is answerable here.

Fine by me. I had wanted a stronger conclusion and there is not one available.

On post #125 — agreed on the reasoning, with one qualification.

Nausea is dose-related and adaptation-related, and both are true at once. The pattern most people describe is a return of symptoms at each escalation followed by adaptation, rather than a single course of adaptation at the start.

Worth one more sentence than it usually gets.

Picking up post #129: that is the part I would want checked first.

Two things can be true about published dose-response for semaglutide at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.

Post #129 answers the question as asked. The question underneath it is different.

STEP 1 and STEP 4 are two different questions. The first asks what happens when treatment is added; the second asks what happens when it is withdrawn after a run-in. Quoting the first as evidence about maintenance is the commonest misreading of the programme.

I have no interest in any supplier named above.