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c/tirzepatide·posted 1 year ago by u/ingrid_correia

[Discussion] dual agonist is doing more work than we give it credit for

Discussion Well Actually ×6

The title is the argument: dual agonist is doing more work than we give it credit for. Here is the rest of it.

The distribution matters more than the mean. In the trial population the interquartile spread was wide enough that two honest people can have completely different runs on the same arm.

Research-use-only material is not approved for human use. Anything in this thread about how a research vial "should" titrate is a discussion about chemistry, not a plan.

Vials and pens carry the same molecule; what differs is fill volume, device tolerance and whether you are doing your own arithmetic. Neither is inherently more accurate.

Corrections welcome, especially the pedantic ones. Pedantry is how this board earns its reputation.

324 up / 14 down96% upvoted27 commentsid 17m8xc26 Sep 2024

27 comments

18 in this archive, depth 5

best — the order this archive was captured in

u/elin_ferrari63 points·1 year ago

The four-week interval in the label is a minimum. Nothing about the pharmacology requires you to step on schedule, and the trials stepped on a calendar because trials have to.

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u/hub_opssite staff53 points·1 year ago

The step schedule question, answered properly, because it comes up weekly.

The label sets a minimum interval of four weeks between increases. That is a floor on how fast you may go, and it exists because tolerability, not efficacy, is what limits most people. There is nothing in the pharmacology that says you must increase at four weeks, or at eight, or ever.

What decides it in practice is whether the effect you want is still there. If appetite is quiet and the trend is going the right way, the dose is doing its job. If both have genuinely gone flat for six weeks or more, that is a conversation worth having with someone who knows your history.

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u/georgi_chowdhury18 points·1 year ago

if 7.5 is working, 10 is not automatically better

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u/samir_falk5 points·1 year ago

SURMOUNT-1 ran 72 weeks with the top arm around 21% mean body weight change. SURPASS is the diabetes programme and reports glycaemic endpoints, so quoting the two interchangeably is a category error.

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u/aurel_lindqvist2 points·1 year ago

zepbound and mounjaro are the same compound with different labels

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u/taper_off_tabitha-26 points·1 year ago

the trials titrated on a calendar, real people titrate on symptoms

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u/teodor_szabo1 point·1 year ago

sulphur burps are the signature complaint and they are not dangerous

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u/ignacio_vanhecke1 point·1 year ago

Yes — 10mg being a genuine landing place for a lot of people is underrated. There is no medal for 15.

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u/nz_unfunded36 points·1 year ago

On comparing yourself with the trial number.

SURMOUNT-1 reported roughly 21% mean body weight change at 72 weeks on the highest arm. Three things get dropped every time that figure is quoted here. It is a mean, and the distribution around it is very wide. It is 72 weeks, which is a year and a half. And it is a trial population with trial support, which is not the same as a person with a spreadsheet.

Use it as a rough shape, not a benchmark. A 12% year is inside the ordinary range and people quit over it every week on this board.

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u/ingrid_correiaOP43 points·1 year ago

Correction to my own post above — I said 12.5mg and I have been on 10mg since the spring. Same argument, wrong number.

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u/blunt_coldbox2924 points·1 year ago

This matches mine. Milder injection-site soreness than I expected, and what there was settled inside a fortnight of each step.

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u/nordic_pricing7 points·1 year ago

dual agonist, so the GIP arm is doing something the sema threads will not tell you about

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u/kaia_cabrera3 points·1 year ago

the four-week step schedule is the label, not folklore

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u/noor_hovland17 points·1 year ago

Appetite effect for me is flat across seven days. On sema it was a wave. Same person, different molecule.

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u/cormac_pereira20 points·1 year ago

the appetite effect is blunter than sema, in a good way, most weeks

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u/emil_okwuosa7 points·1 year ago

pens and vials are the same molecule, the price is the difference

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u/mikkel_ogunleye18 points·1 year ago

the early fullness profile is genuinely gentler than people expect coming from sema

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u/blunt_coldbox2911 points·1 year ago·edited

Did you come to this from sema, and if so how long was the gap?

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Tirzepatide-specific discussion: the dual-agonist pharmacology, the 2.5 → 15mg ladder, the appetite profile people describe as different from semaglutide, and the SURMOUNT/SURPASS trial programme. Comparisons with semaglutide are welcome as long as they are specific about dose equivalence being unknown.

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