The figures, for anyone assembling their own picture. Worth knowing that the injection site changes very little. Abdomen, thigh and upper arm are bioequivalent for semaglutide, so a site change is not a plausible explanation for a bad week.
A narrower follow-up, since the general answer is now clear:
How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?
Dr.PeteFamMed said:Worth knowing that the injection site changes very little.
STEP 5 long-term data on maintenance dosing: the 104-week (2-year) extension showed sustained weight loss of -15.2% with continued semaglutide vs weight regain in the discontinuation group[1].
Key insight: weight loss continued to accrue between weeks 68 and 104 in many patients, suggesting the nadir may not occur until year 2+. The 68-week primary endpoint in most trials may underestimate maximal efficacy.
This supports long-term, open-ended treatment rather than fixed-duration "courses" of therapy.
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Shop Reference StandardsDr.PeteFamMed said:Worth knowing that the injection site changes very little.
Epigenetic implications of GLP-1 therapy and maintenance dosing: emerging evidence suggests that sustained weight loss and metabolic improvement may produce epigenetic changes (DNA methylation, histone modification) that persist beyond drug discontinuation[1].
This is speculative but fascinating: could long-term GLP-1 agonist treatment "reprogram" metabolic gene expression? If so, it would explain why some patients maintain weight loss better than others after discontinuation.
More research needed, but the concept of pharmacologically-induced epigenetic remodeling is intellectually exciting.
Dr.PeteFamMed said:Worth knowing that the injection site changes very little.
This is exactly what I could not find anywhere else. Adding it to my notes with a link back to this thread.