Muscle cramps on semaglutide — 6 month update

HPLC_Greg said:

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

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.

labquiet_amy said:

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

There is a second half to this that has not been said yet. There is also a quality change that the scan cannot see. Weight loss shifts fiber-type distribution toward Type I and improves mitochondrial density and insulin-stimulated glucose uptake per fiber — so the muscle you keep is metabolically better even though there is less of it. That does not make the loss irrelevant, but it explains why function often holds up better than the number suggests.

Following on from JakeSmashed95 — and this may be the naive question:

What fraction of loss being lean mass is actually normal, because the numbers quoted here range from 10% to 40% and cannot all be right?

Reporting back.

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.