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ForumsCardiovascular OutcomesGLP-1 and peripheral arterial disease — looking for input

GLP-1 and peripheral arterial disease — looking for input

dan_philly Thu, Mar 21, 2024 at 8:07 PM 44 replies 3,088 viewsPage 1 of 9
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dan_philly
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Mar 21, 2024 at 8:07 PM#1

Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.

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 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. I have searched first, so if this is covered somewhere point me at it and I will read it.

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.
20 15DadBodDave, AmyNC_wife, SkepticalSean and 17 others
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PharmacoVig_BOS
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Mar 21, 2024 at 8:37 PM#2
dan_philly 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…

Senior perspective on cardiovascular risk: I'm 66 years old and started this journey skeptically. My internist recommended it after years of failed interventions.

8 months later: down 49 lbs, more mobile, pain reduced, medications simplified. My quality of life has improved dramatically. I wish this existed 20 years ago.

To other older adults hesitating: the SELECT trial proved benefit in our age group. You deserve to feel good in your body regardless of age.

19 14Dr.GutHealth, amsterdam_pete, LondonLisa and 16 others
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PurityPaulOR
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Mar 21, 2024 at 9:07 PM#3
dan_philly 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 dan_philly 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.

Last edited: Mar 22, 2024 at 12:07 AM
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ingrid_STO
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Mar 21, 2024 at 9:37 PM#4
PurityPaulOR said:
The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Vitamin deficiency cascade with cardiovascular risk: after 6+ months of reduced food intake, I developed a subtle but important pattern: low B12 → elevated homocysteine → increased cardiovascular risk marker.

The connection: B12 is a cofactor for homocysteine metabolism. Without adequate B12, homocysteine accumulates. This is ironic — taking a CV-protective medication while developing a CV risk factor from reduced nutrition.

Solution: comprehensive vitamin supplementation and regular lab monitoring. Don't let the medication's benefits be undermined by nutritional deficiencies.

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SkepticalSean
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Mar 22, 2024 at 12:24 AM#5
PharmacoVig_BOS said:
Senior perspective on cardiovascular risk: I'm 66 years old and started this journey skeptically.

Can confirm. Same sequence, different timescale.

Last edited: Mar 22, 2024 at 4:24 AM
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