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.
What would genuinely help is knowing whether extending the interval works as well as reducing the dose, since they are not the same intervention pharmacologically.
Tell me what I have not thought of.
This one has a reasonably settled answer, so here it is. STEP 4 is the study that answers this and it is blunt. Participants who continued kept losing; participants switched to placebo regained about two thirds of what they had lost within a year, and the metabolic improvements faded with the weight. That is the same pattern as every other chronic-disease medication ever withdrawn, and it is an argument about the condition rather than about the drug.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
Dr.NutriCornell said:STEP 4 is the study that answers this and it is blunt.
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.
PeptideDetective — Independent Peptide Analytics
Community-driven peptide testing and vendor rating platform. Transparent results. Unbiased analysis. Trusted by thousands.
View ResultsSurmountFan_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.
Same position here, arrived at the long way round. One third of STEP 4 participants held most of their loss without the drug, and nobody has convincingly characterised who they are. That subgroup is the most interesting unanswered question in the field and it is routinely flattened into the two-thirds headline.
Adding the clinical framing, because it changes how the question reads.
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.