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ForumsClinical Trials & ResearchSTEP-HFpEF: semaglutide in heart failure with preserved EF — looking for input Page 2

STEP-HFpEF: semaglutide in heart failure with preserved EF — looking for input

amy_econ_NJ Thu, Mar 19, 2026 at 12:16 PM 12 replies 732 viewsPage 2 of 3
KevinCompounds
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Mar 19, 2026 at 2:32 PM#6
LarryQC_SD said:
The dose-response is real but shallow at the top.

I read this differently from LarryQC_SD, 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.

8 11jennifer_SEA, tyler_CSCS, VanRx_Mike and 5 others
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DataDave
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Mar 19, 2026 at 3:25 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.

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VendorMark
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Mar 19, 2026 at 4:18 PM#8
KevinCompounds 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.

10 13MarkLI_maint, Dr.PeteFamMed, claudia_zurich and 7 others
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steve_okc
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Mar 19, 2026 at 5:10 PM#9

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

How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?

Last edited: Mar 19, 2026 at 9:10 PM
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amy_econ_NJ
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Mar 19, 2026 at 9:22 PM#10

Closing the loop on my own question.

Six weeks on from posting: I stopped reading the weekly number and started reading a four-week average, and the "stall" I opened this thread about was a 1.8kg loss I could not see.

21 21NurseLeah_Nash, gary_naperville, sean_dublin and 18 others
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