Semaglutide cardiovascular benefit: SELECT trial deep dive — looking for input

Taking the question as asked, rather than the general version of it. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.

LarryQC_SD said:

The mechanism that matters here is not stomach emptying, it is central.

Agreed, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.

MaxMetOK said:

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

From the other side of the consultation, briefly.

6 month update on cardiovascular risk: down 37 lbs, off blood pressure meds, A1C normalized. Genuinely life-changing.