Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
What I am after is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
I have searched first, so if this is covered somewhere point me at it and I will read it.
MikeNYC_runner said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
6 month update on cardiovascular risk: down 46 lbs, off blood pressure meds, A1C normalized. Genuinely life-changing.
Dr.SleepRoch said:6 month update on cardiovascular risk: down 46 lbs, off blood pressure meds, A1C normalized.
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.
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View ResultsMikeNYC_runner said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
This matches mine closely enough to be worth saying so out loud. Nothing to add that would improve it.
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.
[1] Marso SP, et al. N Engl J Med. 2016;375(19):1834-1844.