Semaglutide cardiovascular benefit: SELECT trial deep dive — looking for input

From the other side of the consultation, briefly.

Lp(a) and cardiovascular risk: a nuance that matters. Unlike most lipid markers, Lp(a) is 90%+ genetically determined and doesn't really change with weight loss or GLP-1 therapy.

My Lp(a) has remained at 64 nmol/L across all time points. If yours is elevated (>50 nmol/L), you need additional risk mitigation strategies regardless of your GLP-1 response. Don't assume your medication is covering all cardiovascular risk factors.

james_edin said:

Lp(a) and cardiovascular risk: a nuance that matters.

Can confirm. Same sequence, different timescale.

james_edin said:

Lp(a) and cardiovascular risk: a nuance that matters.

I'm 48 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.

10 months later: down 47 lbs, off lisinopril, A1C from 7.4% to 5.2%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.

james_edin said:

Lp(a) and cardiovascular risk: a nuance that matters.

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.

A narrower follow-up, since the general answer is now clear:

How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?