Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
What I am trying to establish is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Not looking for reassurance. Looking for the part I have got wrong.
kate.chem said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
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.
NeuroNate said:SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to 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.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
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View Resultskate.chem said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
Second this.
Clinical perspective, offered as context rather than as advice.
kate.chem said:...cardiovascular risk is just another fad...
I understand the skepticism — we've all seen "miracle" weight loss solutions come and go. But consider what makes GLP-1 agonists different:
- Phase 3 RCTs with thousands of participants (not 20-person pilot studies)
- Published in NEJM, JAMA, Lancet (not press releases)
- Replicated across multiple independent research groups
- Proven cardiovascular and renal benefits beyond weight loss
- Biological mechanism fully characterized at the receptor level
This isn't a fad — it's a new drug class supported by the highest level of clinical evidence. The comparison to past fads is understandable but inappropriate.