Short answer first, then the reasoning. Extending the interval and reducing the dose are pharmacologically different. Reducing the dose lowers the whole exposure curve evenly; extending the interval keeps the peak and drops the trough. Since the appetite effect tracks the trough, interval extension tends to give you good days and bad days rather than a uniformly smaller effect, which most people find harder to live with.
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 have searched first, so if this is covered somewhere point me at it and I will read it.
kate.chem said:Extending the interval and reducing the dose are pharmacologically different.
Agreed on the ranges, with the condition that a single DEXA is not a measurement, it is one draw from a distribution. Hydration status moves the lean compartment by a kilogram or more between scans, so any comparison of scans done at different times of day or different hydration states is noise.
I would rather be corrected than agreed with, if it comes to it.
Sigma-Aldrich — Research-Grade Standards
Certified reference materials, analytical reagents, and research-grade standards for peptide verification. Trusted by laboratories worldwide.
Shop Reference StandardsLindaRN_retired 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 LindaRN_retired describes. 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 That is the same pattern as every other chronic-disease medication ever withdrawn, and it is an argument about the condition rather than about the drug.
From the other side of the consultation, briefly.
LindaRN_retired said:...the STEP extension data on maintenance dosing is concerning...
Let me offer a different interpretation of the same data. Yes, 2/3 of weight was regained after discontinuation. But consider:
- This is consistent with EVERY chronic disease medication ever studied
- 1/3 of patients maintained significant weight loss — who are they and why?
- The metabolic improvements partially persisted even with weight regain
- The data supports long-term treatment, not a "course" of therapy
The takeaway isn't "the drug fails when you stop" — it's "chronic diseases require ongoing treatment." We've always known this.