This one has a reasonably settled answer, so here it is. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.
Started at 0.25mg with a fairly bad first week, held each step the full four weeks, and I am now at 1mg with no side effects worth naming.
What I actually want to know is whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg.
Happy to be told the question itself is wrong.
JessicaH_TX said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
JessicaH_TX has the substance of this right. The condition it depends on is worth stating. 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".
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Browse GL Biochemandrew_nyc said:Started at 0.25mg with a fairly bad first week, held each step the full four weeks, and I am now at 1mg with no side effects worth naming.
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.
Adding the clinical framing, because it changes how the question reads.
andrew_nyc said:...but the FDA says semaglutide...
Interesting point. I want to add some regulatory nuance: the FDA labeling reflects the specific clinical trial data submitted for approval. Real-world clinical practice often extends beyond the FDA label based on emerging evidence and clinical judgment.
Example: semaglutide was first approved for diabetes (Ozempic), then obesity (Wegovy). The molecule didn't change — our understanding of its applications expanded. Similarly, semaglutide may evolve as more data accumulates.