Short answer first, then the reasoning. The mechanism is more central than most summaries suggest. Receptor agonism in the arcuate nucleus activates POMC neurons and inhibits AgRP/NPY signalling, and the downstream MC4R pathway is the same one disrupted in monogenic obesity — convergent genetic evidence that the target is the right one. Peripherally there is glucose-dependent insulin secretion, glucagon suppression and delayed gastric emptying, but the gastric component largely adapts over months while the central effect persists, which is why the durable effect is appetite rather than fullness.
Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
The bit I cannot resolve on my own is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
I have searched first, so if this is covered somewhere point me at it and I will read it.
PurityPaulOR said:The mechanism is more central than most summaries suggest.
Agreed, and the adaptation point cuts both ways: tachyphylaxis to gastric emptying is why tolerability improves, and it is also why people who were relying on physical fullness feel the effect fade while the appetite effect is still working.
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View Resultsbbq_ray_KC said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
Can confirm. Same sequence, different timescale. Posting only so the count is not one.
From the other side of the consultation, briefly.
Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off amlodipine entirely! My cardiologist is thrilled.
If you're on BP meds and losing weight on a GLP-1, monitor your BP at home regularly. Hypotension symptoms (dizziness, lightheadedness when standing) mean your BP meds may need reduction. Don't wait for your next scheduled appointment — call your doctor.