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ForumsCardiovascular OutcomesSTEP-HFpEF: semaglutide in heart failure with preserved EF — 6 month update Page 2

STEP-HFpEF: semaglutide in heart failure with preserved EF — 6 month update

dave_SLC Mon, Dec 22, 2025 at 4:05 PM 12 replies 1,022 viewsPage 2 of 3
julia.endo
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Dec 22, 2025 at 5:42 PM#6
FDA_TrackerJim said:
The dose-response is real but shallow at the top.

This is where I part company with the consensus forming above. 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.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

7 10anna.melb_AU, mark_tokyo, hans_munich and 4 others
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dan_philly
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Philadelphia, PA
Dec 22, 2025 at 6:20 PM#7

One concrete data point for the thread. 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.

8 11AmyNC_wife, SkepticalSean, Dr.CardioMD and 5 others
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jim_asheville
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Asheville, NC
Dec 22, 2025 at 6:58 PM#8
julia.endo said:
The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Coming at julia.endo’s question from a different direction. 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.

9 12NurseAsh_DET, BenResearch_OR, MikeKY_noInsulin and 6 others
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tane_welly
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Dec 22, 2025 at 7:36 PM#9

One thing that is still open after B12Beth’s answer:

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: Dec 22, 2025 at 10:36 PM
10 13marco_milano, pam_columbus, nick_SD_fit and 7 others
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dave_SLC
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Salt Lake City, UT
Dec 22, 2025 at 10:37 PM#10

OP back with an update, since a thread like this is useless without one.

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.

2 2Dr.BariatricHTX, LindaRN_retired
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