Revisiting: Why tirzepatide titration schedules have more steps than semaglutide's posts 91–102

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.

Anyone who has looked at this more carefully, please correct the record.

On post #89 — agreed on the reasoning, with one qualification.

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.

Written in the hope of being told what I have missed.

The titration schedule has more steps than semaglutide's, which reflects the finer gradation used in the clinical programme rather than a pharmacological requirement for smaller steps.

The honest answer is that it depends, and here is what it depends on.

Tirzepatide titration schedules looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.

Adding a note of thanks rather than an opinion. I did not know most of that.

Worth separating two things that post #92 runs together.

SURPASS-2's comparator choice is the criticism that survives. Semaglutide 1.0 mg was the licensed diabetes dose at the time and it was not the highest dose available in the class, so the trial answers a narrower question than the headline implies.

Having read the whole tirzepatide titration schedules 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.

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.

Same conclusion as the reply above, reached differently, which is mildly reassuring.

Categorical response thresholds — the proportion reaching ten, fifteen or twenty per cent reduction — are more persuasive and less informative than the mean. They depend entirely on where the threshold was drawn.

Trying to state the tirzepatide titration schedules position in a way that someone who disagrees would recognise as fair, because I do not think the version in this thread passes that test.

A note on how tirzepatide titration schedules gets discussed rather than on tirzepatide titration schedules itself: the confident posts get the replies and the careful ones get ignored, and the careful ones have been right more often.

Post #98 describes the usual case. This is about the unusual one.

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.

I have no interest in any supplier named above.