Arterial stiffness reduction on GLP-1 — July 2024

pat_auckland 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.

InsuranceTom said:

SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.

InsuranceTom 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.

pat_auckland said:

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

Can confirm. Same sequence, different timescale.

From the other side of the consultation, briefly.

CRP reduction on cardiovascular risk — this is the lab result that excites me most:

Baseline hsCRP: 11.0 mg/L (high cardiovascular risk)
Month 6 hsCRP: 2.5 mg/L (moderate risk)
Month 12 hsCRP: 0.4 mg/L (low risk)

This level of inflammatory marker reduction is comparable to what you'd see with statin therapy. Combined with the weight loss, my 10-year ASCVD risk score dropped from 18% to 5%. My cardiologist is genuinely impressed.