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ForumsCompounding & FormulationCompounded tirzepatide formulation challenges — looking for input

Compounded tirzepatide formulation challenges — looking for input

Dr.EndoIndy Tue, Jul 9, 2024 at 8:50 AM 43 replies 2,583 viewsPage 1 of 9
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Dr.EndoIndy
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Jul 9, 2024 at 8:50 AM#1

Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.

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.

Where I think it is weakest: the subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.

The narrow version of the question is 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. Happy to be told the question itself is wrong.

Note on sourcing:
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.
14 17mia_MS2, LeilaHI, marcus_mpls and 11 others
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Dr.CardioMD
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Jul 9, 2024 at 8:57 AM#2
Dr.EndoIndy 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.

That is correct as far as it goes, and here is where it stops going. 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.

Last edited: Jul 9, 2024 at 2:57 PM
15 18Dr.NephBHM_UK, kim_atl_prep, sarah_TO and 12 others
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MikeFit_NJ
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Jul 9, 2024 at 9:04 AM#3
Dr.EndoIndy 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.EndoIndy, 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.

16 19DeniseRN_TPA, SandraNC_45, Dr.EndoIndy and 13 others
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pat_auckland
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Jul 9, 2024 at 9:11 AM#4

Answering 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.

Ask again with the specifics and you will get a better answer than this one.

17 20MeganSA_TX, LarryQC_SD, wanda_boise and 14 others
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wei_SG
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Jul 9, 2024 at 9:44 AM#5
Dr.CardioMD said:
The GIP arm is doing real work rather than padding the label.

Agreed, and the enforcement dates were staggered by category — 503A first, 503B a few weeks later — because outsourcing facilities have manufactured inventory and clinic contracts to unwind while a 503A makes to order.

Last edited: Jul 9, 2024 at 10:44 AM
18 21JenPlateau, SallyK_inj, CryptoCarl and 15 others
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