Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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.
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.
What I am after is whether anyone has held 10mg long term rather than climbing, and what happened over the following year. Not looking for reassurance. Looking for the part I have got wrong.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
NeuroNate 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.
No disagreement with NeuroNate. One condition attached. 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.
NeuroNate 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.
I read this differently from NeuroNate, 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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View ResultsThis one has a reasonably settled answer, so here it is. 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.ReproEndo 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.
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.