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

Why adding glucagon agonism to an anti-obesity drug is not self-defeating, given that glucagon raises blood glucose?

kevin_tulsa said:

The glucagon component looks paradoxical and is not.

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

The connection: B12 is a cofactor for homocysteine metabolism. Without adequate B12, homocysteine accumulates. This is ironic — taking a CV-protective medication while developing a CV risk factor from reduced nutrition.

Solution: comprehensive vitamin supplementation and regular lab monitoring. Don't let the medication's benefits be undermined by nutritional deficiencies.

kevin_tulsa said:

The glucagon component looks paradoxical and is not.

kevin_tulsa 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.

kevin_tulsa said:

The glucagon component looks paradoxical and is not.

Thank you for spelling out the reasoning rather than just the conclusion. Taking it to my next appointment.

From the other side of the consultation, briefly.

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.

15 months later: down 62 lbs, off lisinopril, A1C from 8.4% to 5.5%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.