VanRx_Mike said:Dr.Martinez said: ...but the FDA says semaglutide...
Same position here, arrived at the long way round. 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".
PurityPaulOR said:The dose-response is real but shallow at the top.
Agreed on the arithmetic, with one condition: holding indefinitely at a dose that is not doing anything is not patience, it is a stall with a nice name. The distinction is whether appetite has changed at all at the current step.
PurityPaulOR said:The dose-response is real but shallow at the top.
Adding the part of the answer the thread has not reached. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.
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Browse GL BiochemOne 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.
Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful.