sophie_paris said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

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.

DanielChem_CHI said:

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

Metabolic syndrome resolution on cardiovascular risk: I went from meeting 5 of 5 diagnostic criteria to meeting ZERO after 10 months of treatment.

The 5 criteria (and my journey):

1. Waist circumference: 49" → 35" ✅ Resolved
2. Triglycerides: 221 → 106 ✅ Resolved
3. HDL: 33 → 53 ✅ Resolved
4. Blood pressure: 141/95 → 119/73 ✅ Resolved
5. Fasting glucose: 116 → 85 ✅ Resolved

Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.

sophie_paris said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

Adding a me-too, because a thread of one person's experience is not much use. I had assumed I was the exception until I read this.

Adding the clinical framing, because it changes how the question reads.

sophie_paris said:

...we don't know the long-term effects of cardiovascular risk...

This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.

However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.

Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.