DanielChem_CHI said:

Vitamin deficiency cascade with cardiovascular risk: after 6+ months of reduced food intake, I developed a subtle but important pattern: low B12 →…

Pushing back on DanielChem_CHI here. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

tane_welly said:

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

I'm 58 years old and want to share my perspective on cardiovascular risk as an older member of this community.

My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.

11 months later: down 58 lbs, off atorvastatin, A1C from 7.6% to 5.5%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.

Dr.KarenChen said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

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.

Following on from PharmD_Rodriguez — and this may be the naive question:

How would you tell the difference between that and the alternative explanation?

Dr.PulmRoch 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.