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 comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
What would genuinely help is knowing whether anyone has held 10mg long term rather than climbing, and what happened over the following year. Numbers rather than impressions, if you have them.
LipidDoc_ATL said:The GIP arm is doing real work rather than padding the label.
That is correct as far as it goes, and here is where it stops going. 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.
LipidDoc_ATL said:The GIP arm is doing real work rather than padding the label.
I read this differently from LipidDoc_ATL, on substance rather than tone. 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.
Happy to go further on any of that.
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Browse GL BiochemShort answer first, then the reasoning. 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.
That is the short version; the long version is somebody else's post.
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 hsCRP is worth reading alongside them. The inflammatory-marker fall is often the most striking change on a panel and it is consistent with the cardiovascular outcome data.