DataDave said:Extending the interval and reducing the dose are pharmacologically different.
The regain framing needs pushing back on. Two thirds regained means one third did not, and the trial provided no ongoing support to either group. Treating regain as pharmacologically inevitable is as unsupported as treating maintenance as automatic.
SurmountFan_IN 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.
Dr.AddMedPHL said:The regain framing needs pushing back on.
Dr.AddMedPHL 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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Shop Reference StandardsA narrower follow-up, since the general answer is now clear:
Whether extending the interval works as well as reducing the dose, since they are not the same intervention pharmacologically?
Closing the loop on my own question.
I went to a lower dose rather than a longer interval on the strength of the trough argument in this thread, and the difference in how even it feels is obvious.