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ForumsSemaglutide (Ozempic / Wegovy)Semaglutide cardiovascular benefit: SELECT trial deep dive — looking for input Page 2

Semaglutide cardiovascular benefit: SELECT trial deep dive — looking for input

MaxMetOK Tue, Dec 17, 2024 at 2:04 PM 56 replies 2,950 viewsPage 2 of 12
TrialTracker_MD
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Dec 18, 2024 at 3:36 PM#6
Dr.GastroMayo said:
The dose-response is real but shallow at the top.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

Happy to go further on any of that.

Last edited: Dec 18, 2024 at 8:36 PM
49 19Dr.EM_Chicago, pete_RVA, CarlaRPh_TPA and 46 others
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DataDave
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Dec 19, 2024 at 1:47 AM#7

Adding the numbers, since they settle part of this. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

Worth separating that from semaglutide, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

48 18mike_nyc, VendorMark, COA_Karl and 45 others
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Dr.RenalNash
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Dec 19, 2024 at 11:58 AM#8
TrialTracker_MD said:
The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

There is a second half to this that has not been said yet. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.

47 17Dr.NutriCornell, pam_stl, wei_SG and 44 others
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KetoKyle
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Dec 19, 2024 at 10:09 PM#9

Following on from A1cHero_PHX — and this may be the naive question:

What the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss?

46 16Dr.GastroMayo, JakeBK_lifts, DerekSJ_a1c and 43 others
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MaxMetOK
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Dec 21, 2024 at 11:03 PM#10

Reporting back.

Following this thread I went back and re-read the extension data properly. The point about trough rather than peak explains the pattern I was seeing on day six, which I had been blaming on the vial.

30 3PurityPaulOR, MaxMetOK, MounjBrad and 27 others
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