Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.
The GIP arm is doing real work rather than padding the label. GIP receptor agonism appears to improve adipose insulin sensitivity and lipid handling, and — counter-intuitively — GIP signalling in the CNS reduces nausea rather than adding to it, which is why tolerability at high total agonism is better than the GLP-1-only comparison would predict. SURPASS-2 is the cleanest head-to-head: tirzepatide beat semaglutide 1mg at every dose tier.
Where I think it is weakest: the follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
So the question, as narrowly as I can put it: whether anyone has held 10mg long term rather than climbing, and what happened over the following year. I have searched first, so if this is covered somewhere point me at it and I will read it.
NeuroNate said:The GIP arm is doing real work rather than padding the label.
Agreeing with NeuroNate, and the qualification matters more than the agreement. Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five. That matters when you are deciding whether a dose step has finished expressing itself.
NeuroNate said:The GIP arm is doing real work rather than padding the label.
Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The "tirzepatide is simply better" summary irritates me. It is better on mean weight loss, and the cardiovascular outcome evidence is far thinner than semaglutide's. If the reason for treating is cardiovascular risk rather than weight, the evidence base points the other way.
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View ResultsAnswering the narrow version, because the broad one does not have a single answer. SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1. Different trials, different populations, so the comparison is indicative rather than decisive — but SURPASS-2 was a genuine head-to-head and it pointed the same way.
Dr.BariatricHTX said:Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five.
Agreed, and the adaptation point cuts both ways: tachyphylaxis to gastric emptying is why tolerability improves, and it is also why people who were relying on physical fullness feel the effect fade while the appetite effect is still working.