Dr.RenalNash said:Dizziness and cardiovascular risk: I was lightheaded for the first 3 weeks.
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.
Dr.RenalNash said:Dizziness and cardiovascular risk: I was lightheaded for the first 3 weeks.
I want to bring up the cardiovascular angle on cardiovascular risk.
The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.
For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.
One thing that is still open after Dr.RenalNash’s answer:
What did you change at the same time, and can you separate the two now?
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Browse GL BiochemSleepDoc_PDX said:I want to bring up the cardiovascular angle on cardiovascular risk.
SleepDoc_PDX said:...we're creating a generation dependent on cardiovascular risk...
I understand the concern, but consider this analogy: are we "creating a generation dependent on" blood pressure medication? Cholesterol medication? Thyroid medication?
Obesity is a chronic disease with biological drivers. Treating it with medication is no different from treating any other chronic condition. The "dependency" framing implies weakness or moral failure — neither of which is accurate.
If ongoing medication is what keeps someone healthy, that's successful treatment, not dependency.
SleepDoc_PDX said:I want to bring up the cardiovascular angle on 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:
| Intervention | NNT | Timeframe |
|---|---|---|
| Semaglutide (MACE) | 67 | 3.3 years |
| Statins primary prevention (MI) | ~100 | 5 years |
| Aspirin secondary prevention | ~77 | 2 years |
These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.