Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
The bit I cannot resolve on my own is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Practical detail welcome, however dull — the duller the better.
NeuroNate 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.
[1] Marso SP, et al. N Engl J Med. 2016;375(19):1834-1844.
InsuranceTom said:SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.
6 month update on cardiovascular risk: down 35 lbs, off blood pressure meds, A1C normalized. Genuinely life-changing.
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View ResultsAdding the clinical framing, because it changes how the question reads.
NeuroNate 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.