Heart rate increase on GLP-1 — November 2025

From the other side of the consultation, briefly.

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.

One thing that is still open after SaraMom3’s answer:

How would you tell the difference between that and the alternative explanation?

claudia_zurich said:

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

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.

claudia_zurich said:

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

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

Baseline hsCRP: 6.0 mg/L (high cardiovascular risk)
Month 6 hsCRP: 1.5 mg/L (moderate risk)
Month 12 hsCRP: 0.7 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 13% to 4%. My cardiologist is genuinely impressed.

Moderator note: the sourcing question belongs in the vendor section and has been split out. Report rather than reply if it drifts again.