VanRx_Mike 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.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
VanRx_Mike said:I want to bring up the cardiovascular angle on cardiovascular risk.
I'm 67 years old and want to share my perspective on cardiovascular risk as an older member of this community.
My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.
12 months later: down 39 lbs, off metoprolol, A1C from 7.8% to 5.4%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.
Following on from VanRx_Mike — and this may be the naive question:
Why adding glucagon agonism to an anti-obesity drug is not self-defeating, given that glucagon raises blood glucose?
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Browse GL Biochemdave_SLC said:I'm 67 years old and want to share my perspective on cardiovascular risk as an older member of this community.
Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history. Results were encouraging:
- NT-proBNP: 62 pg/mL (normal, cardiac function preserved)
- Lp(a): 42 nmol/L (genetic, unchanged — expected)
- ApoB: dropped from 137 to 87 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.
dave_SLC said:I'm 67 years old and want to share my perspective on cardiovascular risk as an older member of this community.
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.