NeuroNate said:

The pharmacokinetics explain nearly every practical question asked here.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

The figures, for anyone assembling their own picture. Numbers worth memorising for this class: Tmax one to three days for the weekly peptides, terminal half-life about a week for semaglutide and about five days for tirzepatide, steady state at four to five half-lives, subcutaneous bioavailability high enough that site choice is irrelevant.

Worth separating that from the pharmacology, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

InsuranceTom said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Metabolic syndrome resolution on cardiovascular risk: I went from meeting 5 of 5 diagnostic criteria to meeting ZERO after 10 months of treatment.

The 5 criteria (and my journey):

1. Waist circumference: 49" → 35" ✅ Resolved
2. Triglycerides: 233 → 113 ✅ Resolved
3. HDL: 33 → 55 ✅ Resolved
4. Blood pressure: 143/91 → 121/75 ✅ Resolved
5. Fasting glucose: 128 → 85 ✅ Resolved

Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.

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

Which effects tachyphylax and which persist, because the answer explains why tolerability improves while the appetite effect keeps working?

Reporting back.

Update — tachyphylaxis to the gastric effect, persistence of the appetite effect. Two curves, and I had been watching the wrong one.