Comparing weight management treatments after stopping GLP-1 medications

The Comparative Effectiveness of Step-down Treatment Options for Weight Management After Discontinuation of Semaglutide and Tirzepatide: a Randomized Controlled Trial (GLP1 Transition Trial)

Phase 4 Interventional WW International Inc · NCT06605703

This study is testing different weight management treatments for people who have recently stopped using GLP-1 medications to see which one helps them lose weight best over 12 weeks.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment225 (estimated)
Ages18 Years and up
SexAll
SponsorWW International Inc Industry-sponsored
Locations1 site (NYC, New York)
Trial IDNCT06605703 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of various treatment options for weight management in individuals who have recently discontinued the use of GLP-1 medications such as semaglutide and tirzepatide. Participants will be randomized to receive one of three interventions: WW Clinic, Bupropion-Naltrexone, or Bupropion-Naltrexone-Metformin. The primary outcome will focus on measuring absolute and percentage weight change over a 12-week period. The study aims to provide insights into optimal weight management strategies following the cessation of these medications.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a history of obesity or overweight and who have been on GLP-1 medications for at least six months.

Not a fit: Patients with a BMI below 26, diabetes, or those who have undergone surgical obesity treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help patients find effective alternatives for weight management after stopping GLP-1 medications.

How similar studies have performed: Other studies have explored weight management strategies after GLP-1 medication discontinuation, but this specific approach is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 18 years or older
* Previous hx of BMI of \>30 or BMI of \>27 with one or more weight related medically qualifying condition (hypertension, dyslipidemia, sleep apnea, cardiovascular disease)
* Currently taking Wegovy, Ozempic, Mounjaro or Zepbound and have been for at least 6 months
* At least 15% body weight loss since taking Wegovy, Ozempic, Mounjaro, or Zepbound
* Willing to stop taking their GLP-1 medication or is discontinuing due to circumstances such as access, cost, coverage, choice, or any other reason
* Ability to provide informed consent prior to any trial-related activities
* Able to read and write in English

Exclusion Criteria:

* BMI \<26 kg/m2
* Diabetes
* Previous surgical obesity treatment
* Currently pregnant or intending to become pregnant during the study
* Not using highly effective contraception during the study period and for 3 months after
* Breastfeeding
* History of seizures or epilepsy
* Current opioid use or in acute opioid withdrawal
* Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs
* History of glaucoma
* Uncontrolled hypertension
* Severe renal impairment and/or Chronic kidney disease stage III or GFR \<60
* Acute hepatitis or liver failure
* Acute or chronic metabolic acidosis, including diabetic ketoacidosis
* Use of antipsychotic medications or opiod analgesics
* Current or previous history of anorexia or bulimia nervosa
* Engagement with vomiting or laxative use within the last 28 days with the aim of controlling their shape or weight
* Current SSRI, SNRI, mood stabilizer, amphetamine, or corticosteroid use
* Current diagnosis of hyper or hypothyroidism or current use of thyroid replacement medicine
* Current use of beta blockers
* Current use of depo shot (medroxyprogesterone acetate) for birth control
* Current diagnosis of Cushing's disease or syndrome
* Current use of Monoamine Oxidase Inhibitors (MAOIs)
* Known hypersensitivity to bupropion, naltrexone, or metformin
* Any other reason rendering a participant unsuitable for trial participation, as determined by a clinician or study investigator

Where this trial is running

NYC, New York

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions ObesityOverweight
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.