EndoResFellow said:NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated with lower BMI also show associations with reduced cardiovascular risk, confirming a causal pathway[1].
This "natural experiment" (people born with genetically higher GLP-1 signaling being leaner and healthier) provides orthogonal evidence supporting the pharmacological approach. When genetic epidemiology, clinical trials, and mechanistic studies all converge, confidence in the therapeutic approach is high.
[1] Zheng SL, et al. Lancet Diabetes Endocrinol. 2023;11(12):869-879.
Dr.KarenChen said:Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off lisinopril entirely!
Thank you for spelling out the reasoning rather than just the conclusion.
EndoResFellow said:NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk 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.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
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View ResultsBethLabQueen said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
BethLabQueen 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.