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ForumsCardiovascular OutcomesHeart failure hospitalization reduction on semaglutide — looking for input

Heart failure hospitalization reduction on semaglutide — looking for input

marcus_mpls Wed, Sep 10, 2025 at 6:31 PM 28 replies 1,408 viewsPage 1 of 6
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marcus_mpls
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Sep 10, 2025 at 6:31 PM#1

Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes. The effect appeared earlier than the weight-loss curve can comfortably explain, which is the basis for arguing that some of the benefit is direct — anti-inflammatory and vascular — rather than purely a consequence of weight.

Where I think it is weakest: the follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.

So the question, as narrowly as I can put it: how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. Numbers rather than impressions, if you have them.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
43 21bbq_ray_KC, oliver_london, tane_welly and 40 others
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Dr.RaviCardio
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Sep 10, 2025 at 6:52 PM#2
marcus_mpls said:
SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.

44 22anna.melb_AU, mark_tokyo, hans_munich and 41 others
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PharmacoVig_BOS
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Sep 10, 2025 at 7:13 PM#3
marcus_mpls said:
SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

Pushing back on marcus_mpls here. 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.

45 23DataDave, Dr.GutHealth, amsterdam_pete and 42 others
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lisa_labSD
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Sep 10, 2025 at 7:34 PM#4

Answering the narrow version, because the broad one does not have a single answer. 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.

46 24lori_vegas, Dr.PulmRoch, maya_sedona and 43 others
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tyler_CSCS
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Sep 10, 2025 at 9:27 PM#5
Dr.RaviCardio said:
All true, with one condition: that curve is for people who reached the dose on schedule.

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

47 0bbq_ray_KC, oliver_london, tane_welly and 44 others
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