Adding the numbers, since they settle part of this. Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.

One thing that is still open after NurseLeah_Nash’s answer:

Whether anyone has held 10mg long term rather than climbing, and what happened over the following year?

bri_stats said:

Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same…

Coming at bri_stats’s question from a different direction. 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 in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes. The effect appeared earlier than the weight-loss curve can comfortably explain, which is the basis for arguing that some of the benefit is direct — anti-inflammatory and vascular — rather than purely a consequence of weight.

Closing the loop on my own question.

I stayed at 10mg. Another six months, another 7kg, no new side effects, and my reading of the dose-response says the last two steps were never going to be worth what they cost me.

chris_chi24 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…

Agreed on the mechanism, with the caveat that the head-to-head used semaglutide 1mg, not 2.4mg. It is still the best direct evidence available, but it is not the comparison most people think they are citing.