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ForumsCardiovascular OutcomesHeart failure hospitalization reduction on semaglutide — 6 month update

Heart failure hospitalization reduction on semaglutide — 6 month update

ricardo_MIA Thu, Feb 22, 2024 at 4:53 AM 17 replies 2,290 viewsPage 1 of 4
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ricardo_MIA
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Feb 22, 2024 at 4:53 AM#1

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.

What I actually want to know is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.

Tell me what I have not thought of.

22 17JakeSmashed95, NauseaFreeNow, SteveThurs and 19 others
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Dr.KarenChen
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Feb 22, 2024 at 6:03 AM#2

Short answer first, then the reasoning. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

Last edited: Feb 22, 2024 at 12:03 PM
21 16JessicaM_2024, TomFromTexas, mike.trainer_LA and 18 others
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emma_london
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Feb 22, 2024 at 7:13 AM#3
Dr.KarenChen said:
The dose-response is real but shallow at the top.

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.

20 15TomFromTexas, mike.trainer_LA, sarah_nash92 and 17 others
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tane_welly
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Feb 22, 2024 at 8:23 AM#4
ricardo_MIA said:
Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

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.

19 14marco_milano, pam_columbus, nick_SD_fit and 16 others
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Dr.LeslieOBGYN
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Feb 22, 2024 at 3:06 PM#5

Clinical perspective, offered as context rather than as advice.

ricardo_MIA said:
...we don't know the long-term effects of cardiovascular risk...

This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.

However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.

Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.

18 13mike_mealprep, NicoleRaleigh, james_edin and 15 others
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