This is the version of the explanation I wish somebody had given me, written down before I forget what confused me. It is about tirzepatide, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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.
The condition it depends on
The caveat that the head-to-head used semaglutide 1mg, not 2.4mg. It is still the best direct evidence available, but it is not the comparison most people think they are citing.
The practical version
Practical numbers: half-life about 5 days, steady state 3 to 4 weeks, ladder 2.5 / 5 / 7.5 / 10 / 12.5 / 15mg, and the maintenance doses with published data behind them are 5, 10 and 15mg.
What I am not sure about
The narrow version of the question is whether anyone has held 10mg long term rather than climbing, and what happened over the following year. Tell me what I have not thought of.
Dr.PainCLE said:SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.
Agreeing with Dr.PainCLE, and the qualification matters more than the agreement. 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.
Dr.PainCLE said:SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.
I read this differently from Dr.PainCLE, 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.
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Browse GL BiochemAnswering the narrow version, because the broad one does not have a single answer. 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.
LarryQC_SD said:The GIP arm is doing real work rather than padding the label.
Agreed, with the caveat that "exercise" for someone with mobility limitations is a different set of options, and the standard advice is written as though everyone can walk for an hour.