Semaglutide cardiovascular benefit independent of weight loss — March 2026

Dr.AddMedPHL said:

Dr.NateNeph said: ...we're creating a generation dependent on cardiovascular risk...

Genuinely useful, thank you. I had the facts and not the framework. Sending this to two other people who asked me the same thing last week.

Closing the loop on my own question.

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me. I was escalating because the number was available, not because I had stopped responding.

KevinCompounds said:

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me.

This matches mine closely enough to be worth saying so out loud. I had assumed I was the exception until I read this.

KevinCompounds said:

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me.

KevinCompounds said:

...cardiovascular risk is just another fad...

I understand the skepticism — we've all seen "miracle" weight loss solutions come and go. But consider what makes GLP-1 agonists different:

• Phase 3 RCTs with thousands of participants (not 20-person pilot studies)
• Published in NEJM, JAMA, Lancet (not press releases)
• Replicated across multiple independent research groups
• Proven cardiovascular and renal benefits beyond weight loss
• Biological mechanism fully characterized at the receptor level

This isn't a fad — it's a new drug class supported by the highest level of clinical evidence. The comparison to past fads is understandable but inappropriate.

KevinCompounds said:

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me.

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.