My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
What would genuinely help is knowing how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
I have searched first, so if this is covered somewhere point me at it and I will read it.
SaraMom3 said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
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.RaviCardio said:Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…
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 ResultsSaraMom3 said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Same experience, arrived at from the opposite direction. Nothing to add that would improve it.
Adding the clinical framing, because it changes how the question reads.
6 month update on cardiovascular risk: down 37 lbs, off blood pressure meds, A1C normalized. Genuinely life-changing.