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 account of SURPASS-2 is wrong? I ask because I have been treating it as settled and I noticed this week that I could not say why.

Working through the consequences rather than the evidence, since others here are better placed on the evidence.

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.

Not the answer, but possibly the question that gets there.

Adding the measurement that the opening post says would settle it.

Injection-site reactions were reported at a low but non-zero rate across the trials. The practical point is that a reaction at one site does not predict a reaction at the next, and rotating properly makes the question moot.

It is worth stating the boring hypothesis before the interesting one.

Quietly grateful for the plain phrasing. Not every thread gets that.

Titration schedules for tirzepatide have more dose steps than semaglutide partly because the compound is more potent and partly because the clinical programme used a finer gradation. That does not mean you cannot escalate on a coarser schedule if that suits you — the published schedule is not a lower bound.

It is worth checking rather than assuming, which costs nothing.