BethLabQueen said:

The dose-response is real but shallow at the top.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.

Adding the numbers, since they settle part of this. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

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

NurseKim_ATL said:

The trial means are being read too generously in this thread.

Coming at NurseKim_ATL’s question from a different direction. FLOW is the relevant trial and it reported a meaningful reduction in kidney-disease progression and related death in people with type 2 diabetes and chronic kidney disease. The mechanism looks to be a mixture of reduced albuminuria, better glycaemia and blood pressure, and a probable direct anti-inflammatory effect on the glomerulus. Separately, eGFR is genuinely noisy during rapid weight loss — a small early dip is common and usually haemodynamic rather than damage.

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

How to read eGFR during rapid weight loss, given that creatinine depends on muscle mass and muscle mass is changing?

Closing the loop on my own question.

Following this thread I went back and re-read the extension data properly. The point about trough rather than peak explains the pattern I was seeing on day six, which I had been blaming on the vial.