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ForumsCardiovascular OutcomesSTEP-HFpEF: semaglutide in heart failure with preserved EF — March 2026 Page 2

STEP-HFpEF: semaglutide in heart failure with preserved EF — March 2026

GenomicsKate Wed, Jun 4, 2025 at 7:34 PM 38 replies 1,967 viewsPage 2 of 8
HPLC_Greg
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Jun 6, 2025 at 5:22 AM#6
NeuroNate said:
Steady state is the thing most people miss.

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.

Last edited: Jun 6, 2025 at 11:22 AM
5 8SallyK_inj, CryptoCarl, MariaRD and 2 others
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FDA_TrackerJim
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Jun 6, 2025 at 6:52 PM#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.

Happy to go further on any of that.

6 9Admin, Dr.Martinez, mike_mod and 3 others
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claudia_zurich
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Jun 7, 2025 at 8:23 AM#8
HPLC_Greg said:
The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Adding the part of the answer the thread has not reached. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.

7 10Dr.LipidDallas, alex_tucson, kevin_tulsa and 4 others
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nancy_portland
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Jun 7, 2025 at 9:54 PM#9

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

Whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg?

Last edited: Jun 7, 2025 at 10:54 PM
8 11Dr.PeteFamMed, claudia_zurich, nancy_portland and 5 others
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GenomicsKate
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Jun 10, 2025 at 2:48 PM#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.

14 14claudia_zurich, nancy_portland, rick_sfbay and 11 others
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