MounjBrad 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…

MounjBrad 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.

MounjBrad 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…

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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.

SarahChen_PharmD 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.

Dr.GutHealth said:

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

Same pattern here, and in the same order.