Arterial stiffness reduction on GLP-1 — July 2024

Dr.KarenChen said:

Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off lisinopril entirely!

NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).

From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.

Compare to established therapies:

These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.

PedsEndoPhilly said:

InsuranceTom said: ...cardiovascular risk is just another fad...

Thank you for spelling out the reasoning rather than just the conclusion. I will report back once I have actually tried it.

Dr.KarenChen said:

Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off lisinopril entirely!

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.

pat_auckland said:

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

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.

Moderator note: a couple of off-topic posts removed. Carry on.