Dr.CardioMD said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

Dr.CardioMD said:

...we're creating a generation dependent on cardiovascular risk...

I understand the concern, but consider this analogy: are we "creating a generation dependent on" blood pressure medication? Cholesterol medication? Thyroid medication?

Obesity is a chronic disease with biological drivers. Treating it with medication is no different from treating any other chronic condition. The "dependency" framing implies weakness or moral failure — neither of which is accurate.

If ongoing medication is what keeps someone healthy, that's successful treatment, not dependency.

Dr.CardioMD said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

This is where I part company with the consensus forming above. 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.

amsterdam_pete said:

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

NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).

From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.

Compare to established therapies:

These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.

mike.trainer_LA said:

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

Can confirm. Same sequence, different timescale. I had assumed I was the exception until I read this.