GLP-1 discontinuation: weight regain trajectory and mitigation strategies

Dr.ObesityMed

VIP Member

3,456

19,234

Nov 2023

Denver, CO

Online

Apr 23, 2026 at 9:31 PM#1

Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.

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.

Where I think it is weakest: the completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.

So the question, as narrowly as I can put it: whether there is a lowest maintenance dose with actual maintenance data behind it, or whether everything published sits at the top of the ladder. Tell me what I have not thought of.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.

33 3EndoResFellow, PharmacoVig_BOS, SurmountFan_IN and 30 others

Reply Quote Save Share Report

Dr.LipidDallas

VIP Member

2,678

14,567

Dec 2023

Dallas, TX

Apr 23, 2026 at 10:59 PM#2

Dr.ObesityMed said:
Extending the interval and reducing the dose are pharmacologically different.

No disagreement with Dr.ObesityMed. One condition attached. 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 That is the same pattern as every other chronic-disease medication ever withdrawn, and it is an argument about the condition rather than about the drug.

Happy to go further on any of that.

Last edited: Apr 24, 2026 at 12:59 AM

32 2wei_SG, cory_ATX, lori_vegas and 29 others

Reply Quote Save Share Report

Dr.RenalNash

VIP Member

1,234

7,890

Mar 2024

Nashville, TN

Apr 24, 2026 at 12:27 AM#3

Dr.ObesityMed 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.

Ask again with the specifics and you will get a better answer than this one.

Last edited: Apr 24, 2026 at 5:27 AM

31 1Dr.NutriCornell, pam_stl, wei_SG and 28 others

Reply Quote Save Share Report

PeptideMeter — Independent Peptide Analytics

Community-driven peptide testing and vendor rating platform. Transparent results. Unbiased analysis. Trusted by thousands.

View Results

traveltech_sara

Member

156

678

Jan 2025

Remote, USA

Apr 24, 2026 at 1:55 AM#4

Answering the narrow version, because the broad one does not have a single answer. 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.

30 0NurseAsh_DET, BenResearch_OR, MikeKY_noInsulin and 27 others

Reply Quote Save Share Report