LipidDoc_ATL said:The GIP arm is doing real work rather than padding the label.
Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows:
Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill coefficient ≈ 1.3
Tirzepatide: ED50 ≈ 6mg, Emax ≈ -25%, Hill coefficient ≈ 1.5
Clinical implication: most patients achieve >80% of maximal response by the mid-range dose (1.7mg sema, 10mg tirz). Going to the maximum dose provides diminishing returns — possibly not worth the additional side effect burden for some patients. Individualize dosing based on response vs tolerability.
Following on from jim_asheville — and this may be the naive question:
How much of the tirzepatide advantage is the GIP component and how much is simply that the dose ladder goes higher in receptor-occupancy terms?
jason_paloalto said:Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows: Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill…
Coming at jason_paloalto’s question from a different direction. ApoB is the more informative number and it is cheap. LDL-C estimates cholesterol mass in atherogenic particles; ApoB counts the particles, and it is particle count that tracks risk — which is why the two can disagree and why the disagreement is the clinically interesting case. Triglycerides fall substantially with weight loss and improved insulin sensitivity, HDL moves modestly, and LDL-C often barely moves at all, which surprises people who expected everything to improve together.
Worth separating that from the lipid panel, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.
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Update: the eight-week restart pattern people described is exactly what happened. I nearly abandoned it at week five.
chris_chi24 said:ApoB is the more informative number and it is cheap.
True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.
Correct me if the detail matters more than I have assumed.