I am eight weeks into deliberately reducing rather than stopping, and the appetite change came back faster than the weight did.
The bit I cannot resolve on my own is whether extending the interval works as well as reducing the dose, since they are not the same intervention pharmacologically.
I would rather have one careful answer than five confident ones.
Short answer first, then the reasoning. 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 That is the same pattern as every other chronic-disease medication ever withdrawn, and it is an argument about the condition rather than about the drug.
Ask again with the specifics and you will get a better answer than this one.
LabKate said:STEP 4 is the study that answers this and it is blunt.
All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.
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Shop Reference StandardsInsuranceTom said:I am eight weeks into deliberately reducing rather than stopping, and the appetite change came back faster than the weight did.
Can confirm the pattern InsuranceTom describes. 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.
From the other side of the consultation, briefly.
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.