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ForumsCardiovascular OutcomesSTEP-HFpEF: semaglutide in heart failure with preserved EF — what worked for you? Page 2

STEP-HFpEF: semaglutide in heart failure with preserved EF — what worked for you?

Dr.GutHealth Fri, Aug 30, 2024 at 4:44 AM 10 replies 1,930 viewsPage 2 of 2
Dr.NateNeph
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Aug 30, 2024 at 10:03 AM#6
sarah.morrison said:
The mechanism that matters here is not stomach emptying, it is central.

I read this differently from sarah.morrison, on substance rather than tone. 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.

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

36 6JakeSmashed95, NauseaFreeNow, SteveThurs and 33 others
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LabKate
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Aug 30, 2024 at 12:08 PM#7

The figures, for anyone assembling their own picture. 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.

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Dr.RenalNash
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Aug 30, 2024 at 2:13 PM#8
Dr.NateNeph 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 dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

34 4Dr.NutriCornell, pam_stl, wei_SG and 31 others
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fiona_VT
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Aug 30, 2024 at 4:18 PM#9

A narrower follow-up, since the general answer is now clear:

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

Last edited: Aug 30, 2024 at 5:18 PM
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Dr.GutHealth
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Aug 31, 2024 at 2:17 AM#10

Closing the loop on my own question.

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.

5 3MikeKY_noInsulin, Dr.RaviCardio, jennifer_SEA and 2 others
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