Dr.MetabolicMD said:Lp(a) and cardiovascular risk: a nuance that matters.
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.
CanadaChris said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk. In 3,297 T2DM patients with high CV risk: MACE HR 0.74 (95% CI 0.58-0.95, p=0.02)[1].
Notable: the retinopathy signal in SUSTAIN-6 (HR 1.76) was subsequently attributed to rapid A1C reduction in patients with pre-existing retinopathy — not a direct drug effect. This has been confirmed in longer-term follow-up studies.
[1] Marso SP, et al. N Engl J Med. 2016;375(19):1834-1844.
anders_CPH said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
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.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
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Browse GL BiochemA narrower follow-up, since the general answer is now clear:
Was that from a primary source or from a summary of one?
claudia_zurich said:Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling,…
Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history. Results were encouraging:
- NT-proBNP: 45 pg/mL (normal, cardiac function preserved)
- Lp(a): 25 nmol/L (genetic, unchanged — expected)
- ApoB: dropped from 155 to 85 mg/dL (excellent response)
- Coronary calcium score: 0 (unchanged from baseline — reassuring)
The ApoB reduction is particularly meaningful — it's considered the best single predictor of cardiovascular risk. GLP-1 therapy seems to improve this consistently.