Can you keep the weight off after stopping GLP-1 drugs? scientists test three exit plans
NCT ID NCT07832084
First seen Sep 21, 2026 · Last updated Sep 21, 2026
Summary
Many people who lose weight with GLP-1 drugs like semaglutide or tirzepatide face a choice: stay on the drug indefinitely or stop and risk regaining the weight. This pilot trial compares three approaches in 60 adults with obesity who have reached or nearly reached their target weight. One group keeps the full GLP-1 dose, one tapers to a lower or less frequent dose, and one switches to a non-GLP-1 combination of bupropion and naltrexone. All participants also get a home strength exercise plan to help preserve muscle. Researchers will track weight, side effects, and whether enough people stick with the study to justify a larger trial.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- GLP-1 obesity drugs such as semaglutide and tirzepatide, plus bupropion and naltrexone as an alternative
- What this could lead to
- If tapering or switching works, people who reach their weight goal on GLP-1 drugs could keep the weight off with less medication, lower costs, and fewer side effects.
- What could go wrong
- This is a small pilot study of 60 people, so it can only show whether a larger trial is practical, not whether any strategy truly works. Weight may return when the drug dose drops, and the alternative drug combination has its own side effects.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 4
Runs after approval, following long-term safety and how well the treatment works in everyday use.
- Participants
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About 60 people
The number the study aims to enrol. It can still change while the study runs.
- Expected to start
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Nov 2026
An estimate. Start dates often move.
- Expected to finish
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Sep 2028
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Participant Inclusion Criteria: * Aged18 years or older. * Able to provide informed consent. * Pre-treatment diagnosis of obesity (BMI≥30kg/m2). * On a high potency GLP-1 based therapy (defined as semaglutide ≥1.7 mg or tirzepatide≥10mg). * Has achieved, or are close to achieving, a "target body weight." Target body weight will be defined by each individual patient through self-report or their treating clinician but should generally be at least 5% below their weight prior to first starting GLP-1 based therapy. * Has been on an incretin-based weight loss therapy for at least 6 months. Participant Exclusion Criteria: * Diagnosis of type 2 diabetes or pre-existing cardiovascular disease. * Pregnancy or nursing or are seeking to become pregnant in the next year. * Have had bariatric surgery. * Unwilling to reduce the dose of their GLP-1 medication for weight loss, or who are unwilling to switch to another non-GLP-1based weight loss medication. * Contraindications to bupropion/naltrexone: chronic opioid use, seizure disorders, use of other bupropion containing products, uncontrolled hypertension, monoamine oxidase inhibitors. * Hyperthyroidism. * Glaucoma, or at risk for glaucoma. * History of substance use disorder. * History of suicidal ideation. * Concomitant monoamine oxidase inhibitors within 14 days. * Use of lithium. * Use of metformin.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
1 site. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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University of Pittsburgh
Pittsburgh, Pennsylvania, 15232, United States
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