TomTeleRx 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 TomTeleRx. 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.

TomTeleRx 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 TomTeleRx, 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.

This 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.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

Dr.LipidDallas 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 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.