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ForumsCardiovascular OutcomesSTEP-HFpEF: semaglutide in heart failure with preserved EF — March 2026 Page 3

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 3 of 8
JessicaH_TX
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Jun 13, 2025 at 7:30 AM#11
claudia_zurich said:
Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

Agreed, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.

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

13 13wendy_avl, jason_paloalto, Dr.LeslieOBGYN and 10 others
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MaxMetOK
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Jun 16, 2025 at 12:11 AM#12
DeniseRN_TPA said:
The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people…

That reframing is the part I needed. Taking it to my next appointment.

Last edited: Jun 16, 2025 at 5:11 AM
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SaraMom3
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Jun 18, 2025 at 4:51 PM#13
claudia_zurich said:
Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

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

Last edited: Jun 18, 2025 at 8:51 PM
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wendy_avl
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Jun 21, 2025 at 9:29 AM#14
GenomicsKate said:
Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].

Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.

These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.

References:
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
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mike_mod
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Jun 24, 2025 at 2:06 AM#15

Moderator note: a post naming a supplier has been edited. Discuss suppliers in the review sections, not here. Report rather than reply if it drifts again.

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