Clinical and Neurobehavioral Changes With Weight Loss Drug Discontinuation and Reinitiation

What Was Tested

The trial (not phased) is built around Tirzepatide.

The goal of this clinical study with research procedures is to learn how stopping and restarting tirzepatide (a medication that helps regulate blood sugar and appetite) affects brain activity, behavior, and health in adults ages 18-70 who are currently taking tirzepatide.

Specifically, the study aims to examine how a short pause in tirzepatide affects hunger, mood, sleep, and daily functioning; how stopping and restarting tirzepatide alters brain chemistry and brain responses to food-related images; and how these changes relate to health measures such as quality of life and emotional well-being.

There is no comparison group; instead, researchers will assess changes within each participant across three time points: while taking tirzepatide, after stopping it for 3-4 weeks, and after restarting it for 6-8 weeks.

It had 1 arm (groups): Tirzepatide Discontinuation and Re-Initiation Arm (experimental).

Participants in this single-group arm will complete three study visits that occur while they are taking tirzepatide, during a 3-4 week pause from the medication, and after they restart tirzepatide for 6-8 weeks. All medication changes are supervised by a study physician. At each visit, participants will complete interviews, questionnaires, cognitive tasks, magnetic resonance imaging (MRI) brain scans, and provide stool samples. They will also complete two short check-in phone calls and an online BrainHealth Index assessment between visits.

The registry classes the interventions as other.

More on the Plan

This study specifically recruits individuals currently being prescribed for tirzepatide.

The experimental design will consist of a brief discontinuation of the drug for roughly 3-4 weeks followed by a reinitiation of the medication.

Prescription and administration of tirzepatide is done as part of normal patient care and is not a component of the study.

Who Took Part

40 planned participants were the target.

It was open to people of any sex aged from 18 years up to 70 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Aged 18-70 years. Currently on tirzepatide. Cognitively capable of understanding and signing informed consent. Be proficient in English.

The full record lists 5 inclusion and 20 exclusion criteria; among the exclusions: diagnosis of type 2 diabetes; current diagnosis of an eating disorder; use of medications affecting weight other than tirzepatide.

How the Study Was Run

Design: single-group and open-label.

Being open-label, the Tirzepatide study did not mask who received what.

Everyone received the same intervention, so there was no separate comparison group inside the trial.

It started in 2026-10 with completion listed for 2028-02.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Researchers chose this as the main measure: Change From On-Treatment to Discontinuation and Re-Initiation in Food Cue-Evoked BOLD Response in Reward and Salience Brain Regions (time frame: Baseline (on tirzepatide), 3-4 weeks of discontinuation, and 6-8 weeks of re-initiation).

It also tracked 26 secondary outcomes, for example Change From Baseline in Resting-State Functional Connectivity Within Salience and Executive Control Networks, Change From Baseline in Brain Glutamate Levels, Change From Baseline in State Food Craving Severity, Change From Baseline in Blood-Brain Permeability Levels, Change From Baseline in Trait Food Craving Severity and Change From Baseline in Addictive-Like Eating Symptoms.

What This Means in Plain Language

Put simply, this is a not phased trial of Tirzepatide in 40 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Tirzepatide compound page, all human trials.