DebRD_ATL said:The dose-response is real but shallow at the top.
Pushing back on DebRD_ATL 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.
One concrete data point for the thread. 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.
sarah.morrison said:The trial means are being read too generously in this thread.
Adding the part of the answer the thread has not reached. The liver data is among the strongest non-weight findings in the class. The semaglutide MASH programme reported a large advantage over placebo on MASH resolution, with a substantial minority also achieving fibrosis improvement — and fibrosis is the endpoint that predicts outcomes. Mechanistically it is reduced hepatic lipogenesis, increased fatty-acid oxidation, less hepatic inflammation, and possibly a direct effect on stellate-cell activation.
Ask again with the specifics and you will get a better answer than this one.
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Browse GL BiochemA narrower follow-up, since the general answer is now clear:
Whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is?
Closing the loop on my own question.
Six weeks on from posting: I stopped reading the weekly number and started reading a four-week average, and the "stall" I opened this thread about was a 1.8kg loss I could not see.