Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.
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.
Happy to be told the question itself is wrong.
carl_compliance said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
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.
JessicaH_TX said:I want to bring up the cardiovascular angle on cardiovascular risk.
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.
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Browse GL Biochemcarl_compliance said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
This is my experience too, for whatever a second data point is worth.
Clinical perspective, offered as context rather than as advice.
6 month update on cardiovascular risk: down 41 lbs, off blood pressure meds, A1C normalized. Genuinely life-changing.