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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

Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using 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 completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.

What would genuinely help is knowing how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. Practical detail welcome, however dull — the duller the better.

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.SleepRoch
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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…

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.

Last edited: Sep 10, 2025 at 10:52 PM
44 22kim_atl_prep, sarah_TO, wendy_avl and 41 others
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SarahChen_PharmD
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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…

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.

45 23paul_denver, TinaHashiRN, robert_kc and 42 others
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paige_pharma
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Sep 10, 2025 at 7:34 PM#4

Short answer first, then the reasoning. 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.

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

46 24lisa_labSD, adam_van, Dr.SurgeonPGH and 43 others
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dave_SLC
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Sep 10, 2025 at 9:27 PM#5
Dr.SleepRoch said:
The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people…

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.

47 0Dr.BariatricHTX, LindaRN_retired, tommy_boulder and 44 others
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