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

On post #117 — agreed on the reasoning, with one qualification.

Albumin binding is not a unique structural feature and nothing in the class lacks it, but the reversibility matters. Semaglutide binds albumin covalently through a fatty side chain, which creates a very long half-life at the cost of sequestering the free form. That is a trade-off and it is the trade-off that allows weekly dosing.

Is there a ceiling dose beyond which the effect plateaus? The trials did not study that because they stopped at 2.4 mg. Some people report trying higher doses, but trial data is absent and off-label dosing enters territory this site does not advise on.

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.

Picking up post #121: that is the part I would want checked first.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

The STEP programme populations were selected: enrollment criteria required baseline body mass index over 30, no recent blood pressure crisis, no recent retinopathy, no renal disease at the time. Applying results from that population to someone well outside it is an extrapolation and should be called one.

I read post #125 twice before replying, because I had assumed the opposite.

The mass figure differs between sources because of how the different entities report it. The monoisotopic mass of the bare peptide is one number; the mass including the acylation is another. Different sources emphasise different details.

This follows post #125 rather than contradicting it.

Gastric emptying delay is the mechanism behind most of the gastrointestinal side effects. Slowing the stomach empties it feeds less food into the intestines at a time, which is part of the satiety mechanism but is also why nausea is dose-dependent and titration-dependent.

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

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.

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

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

Picking up post #128: that is the part I would want checked first.

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.