james_edin said:Pregnancy after maintenance dosing weight loss: stopped GLP-1 medication 4 months before TTC as recommended.
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.
[1] Garvey WT, et al. Nat Med. 2022;28:2083-2091.
james_edin said:Pregnancy after maintenance dosing weight loss: stopped GLP-1 medication 4 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.
A narrower follow-up, since the general answer is now clear:
Whether resistance training and protein change the ratio or only the absolute amount?
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Shop Reference StandardsLabKate said:The concept of "metabolic set point" and its relevance to maintenance dosing: the body actively defends a weight set point through hormonal feedback…
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.
LabKate said:The concept of "metabolic set point" and its relevance to maintenance dosing: the body actively defends a weight set point through hormonal feedback…
Agreed, and the size of the effect matters as much as its existence. Something real and small gets treated here as though it were real and decisive.