Dr.SportsMedIN said:

Amylin analogues act on a different satiety circuit — area postrema and dorsal raphe — rather than the arcuate pathway GLP-1 agonists use.

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.

Dr.SportsMedIN said:

Amylin analogues act on a different satiety circuit — area postrema and dorsal raphe — rather than the arcuate pathway GLP-1 agonists use.

Pushing back on Dr.SportsMedIN here. Two drugs, two side-effect profiles, one price. The efficiency argument only works if the tolerability really is better than dose-escalating a single agent, and I have not seen that demonstrated head to head.

Short answer first, then the reasoning. The pharmacokinetics explain nearly every practical question asked here. Albumin binding above 99% slows clearance enough to make weekly dosing possible; a terminal half-life near a week means four to five weeks to steady state and therefore a four-week titration interval; subcutaneous bioavailability around 89% means injection site barely matters. Those three facts answer most timing questions before they are asked.

sarah.morrison said:

Agreed, and the adaptation point cuts both ways: tachyphylaxis to gastric emptying is why tolerability improves, and it is also why people who were…

Adding a me-too, because a thread of one person's experience is not much use. Posting only so the count is not one.