pat_auckland said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.

PharmHunterJen said:

Agreed, though "tolerable" needs defining.

This is exactly what I could not find anywhere else. Adding it to my notes with a link back to this thread.

pat_auckland said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

Correct me if the detail matters more than I have assumed.

Dr.Martinez said:

I am eight weeks into deliberately reducing rather than stopping, and the appetite change came back faster than the weight did.

Dr.Martinez said:

...I stopped maintenance dosing and regained all the weight...

This is a really important data point and I appreciate your honesty. The STEP 1 extension data showed ~2/3 of weight regain within 12 months of discontinuation.

This doesn't mean the drug "doesn't work" — it means obesity is a chronic disease requiring ongoing treatment, just like hypertension or diabetes. We don't criticize blood pressure meds for "not working" when BP rises after stopping them.

The framing matters. maintenance dosing is a treatment, not a cure. And that's okay.

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part.