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A Randomized Controlled Trial Comparing the Effectiveness of Different Treatment Options for Weight Management After Discontinuation of Semaglutide and Tirzepatide (GLP1 Transition Trial)

A Randomized Controlled Trial Comparing the Effectiveness of Different Treatment Options for Weight Management After Discontinuation of Semaglutide and Tirzepatide (GLP1 Transition Trial)

Recruiting
18 years and older
All
Phase 4

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Overview

The study compares the effectiveness of treatment options for weight management after discontinuing semaglutide and tirzepatide. The primary outcome is absolute and percentage weight change at 12-weeks.

Eligibility

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 <22 kg/m2
  • Diabetes
  • Previous surgical obesity treatment
  • Currently pregnant or intending to become pregnant during the study
  • 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

Study details
    Obesity
    Overweight

NCT06605703

Michelle Cardel, PhD, MS, RD

21 October 2025

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