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Evidence-based GLP-1 & peptide discussion since 2023
ForumsCardiovascular OutcomesMy dad had a heart attack and now I am terrified - will GLP-1 help? — looking for input Page 3

My dad had a heart attack and now I am terrified - will GLP-1 help? — looking for input

PharmHunterJen Thu, Jul 3, 2025 at 12:34 AM 37 replies 2,232 viewsPage 3 of 8
FranDenver
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Jul 4, 2025 at 2:00 AM#11
NurseKim_ATL said:
Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…

Genuinely useful, thank you. I had the facts and not the framework. Printing the relevant bit and taking it with me.

46 21Dr.RenalNash, LipidDoc_ATL, BariatricNurseD and 43 others
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sean_dublin
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Jul 4, 2025 at 11:44 AM#12

From the other side of the consultation, briefly.

I want to bring up the cardiovascular angle on cardiovascular risk.

The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.

For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.

References:
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.
Last edited: Jul 4, 2025 at 12:44 PM
45 20sean_dublin, hannah_MT, Dr.SportsMedIN and 42 others
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CarlaRPh_TPA
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Jul 4, 2025 at 9:28 PM#13
JenPlateau said:
josh_phd_bmore said: ...we don't know the long-term effects of cardiovascular risk...
JenPlateau said:
...we're creating a generation dependent on cardiovascular risk...

I understand the concern, but consider this analogy: are we "creating a generation dependent on" blood pressure medication? Cholesterol medication? Thyroid medication?

Obesity is a chronic disease with biological drivers. Treating it with medication is no different from treating any other chronic condition. The "dependency" framing implies weakness or moral failure — neither of which is accurate.

If ongoing medication is what keeps someone healthy, that's successful treatment, not dependency.

Last edited: Jul 5, 2025 at 1:28 AM
44 19BrianDallas92, labquiet_amy, emily_PDX and 41 others
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Dr.GutHealth
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Jul 5, 2025 at 7:12 AM#14
PharmHunterJen 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…

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.
43 18Dr.RaviCardio, jennifer_SEA, tyler_CSCS and 40 others
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Admin
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Jul 5, 2025 at 4:56 PM#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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