GenomicsKate said:nancy_portland said: ...we don't know the long-term effects of cardiovascular risk...
Same pattern here, and in the same order. Posting only so the count is not one.
SleepDoc_PDX said:SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.
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.
One thing that is still open after SleepDoc_PDX’s answer:
Whether anyone has held 10mg long term rather than climbing, and what happened over the following year?
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View ResultsDr.GutHealth said:I want to bring up the cardiovascular angle on cardiovascular risk.
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.
Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful.