Dr.NutriCornell said:Pregnancy after maintenance dosing weight loss: stopped GLP-1 medication 5 months before TTC as recommended.
The concept of "metabolic set point" and its relevance to maintenance dosing: the body actively defends a weight set point through hormonal feedback (leptin, ghrelin, insulin, GLP-1). After weight loss, these signals shift to promote weight regain[1].
GLP-1 agonists may work in part by resetting this set point — or at least overriding the counter-regulatory signals that drive regain. This would explain why continued treatment maintains weight loss while discontinuation leads to regain.
Understanding maintenance dosing through this lens reframes the drug from "weight loss tool" to "metabolic set point modulator."
[1] Rosenbaum M, et al. J Clin Invest. 2008;118(7):2583-2591.
jennifer_SEA said: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…
Bookmarking. The distinction being drawn above is the one nobody else makes. I will report back once I have actually tried it.
Dr.NutriCornell said:Pregnancy after maintenance dosing weight loss: stopped GLP-1 medication 5 months before TTC as recommended.
Dr.NutriCornell said:...I stopped maintenance dosing and regained all the weight...
This is a really important data point and I appreciate your honesty. The STEP 1 extension data showed ~2/3 of weight regain within 12 months of discontinuation.
This doesn't mean the drug "doesn't work" — it means obesity is a chronic disease requiring ongoing treatment, just like hypertension or diabetes. We don't criticize blood pressure meds for "not working" when BP rises after stopping them.
The framing matters. maintenance dosing is a treatment, not a cure. And that's okay.
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Browse GL BiochemAttorneyGrant said:Planning the end of this rather than the middle of it, which nobody around me seems to want to talk about while it is still going well.
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.
[1] Ling C, et al. Diabetologia. 2023;66(6):1078-1093.
Moderator note: leaving this open. It is being argued well and the disagreement is the useful part. Thread quality here is what the rules are for. Keep it up.