My cardiologist just high-fived me at my checkup lol — July 2024

NeuroNate said:

Metabolic syndrome resolution on cardiovascular risk: I went from meeting 5 of 5 diagnostic criteria to meeting ZERO after 13 months of treatment.

Pushing back on NeuroNate 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.

MASHdoc_SA said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].

Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.

These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.

KevinCompounds said:

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

KevinCompounds said:

...we don't know the long-term effects of cardiovascular risk...

This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.

However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.

Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.

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

How long did you give it before you decided it was working?

Dr.ObesityLA said:

KevinCompounds said: ...we don't know the long-term effects of cardiovascular risk...

Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off metoprolol 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.