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

Inclusion Criteria:

• 18 years or older

• Previous hx of BMI of >30 or BMI of >27 with one or more weight related medicallyqualifying condition (hypertension, dyslipidemia, sleep apnea, cardiovasculardisease)

• Currently taking Wegovy, Ozempic, Mounjaro or Zepbound and have been for at least 6months

• 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 tocircumstances 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, antiepilepticdrugs

• 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 ofcontrolling their shape or weight

• Current SSRI, SNRI, mood stabilizer, amphetamine, or corticosteroid use

• Current diagnosis of hyper or hypothyroidism or current use of thyroid replacementmedicine

• 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, asdetermined by a clinician or study investigator