My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
The narrow version of the question is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Happy to be told the question itself is wrong.
DanielChem_CHI said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
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.
TrialTracker_MD said:I want to bring up the cardiovascular angle on cardiovascular risk.
Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off amlodipine entirely! My cardiologist is thrilled.
If you're on BP meds and losing weight on a GLP-1, monitor your BP at home regularly. Hypotension symptoms (dizziness, lightheadedness when standing) mean your BP meds may need reduction. Don't wait for your next scheduled appointment — call your doctor.
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View ResultsDanielChem_CHI said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Mine went the same way, slower. Posting only so the count is not one.
Clinical perspective, offered as context rather than as advice.
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.