Insomnia on semaglutide — anyone have experience?

hyun_seoul said:

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

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

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

hyun_seoul said:

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

Pushing back on hyun_seoul here. 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.

Short answer first, then the reasoning. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

PharmD_Rodriguez said:

The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people…

Agreed, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.