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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Behavioral: WW Clinic; Drug: Bupropion-Naltrexone; Drug: Bupropion-Naltrexone-Metformin

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10011
      • WW International, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WW Clinic - No medications; Participants in this group receive behavioral or lifestyle support from WW Clinic. They receive no medications.	Behavioral: WW Clinic; Telehealth platform that specializes in medical weight management and integrates the behavioral and lifestyle support from WW.
Experimental: WW Clinic + Meds v1; Participants in this group receive behavioral or lifestyle support from WW Clinic. They receive medications prescribed through WW Clinic.	Behavioral: WW Clinic; Telehealth platform that specializes in medical weight management and integrates the behavioral and lifestyle support from WW.; Drug: Bupropion-Naltrexone; Bupropion-Naltrexone
Experimental: WW Clinic + Meds v2; Participants in this group receive behavioral or lifestyle support from WW Clinic. They receive medications prescribed through WW Clinic.	Behavioral: WW Clinic; Telehealth platform that specializes in medical weight management and integrates the behavioral and lifestyle support from WW.; Drug: Bupropion-Naltrexone-Metformin; Bupropion-Naltrexone-Metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent body weight change at 12 weeks	Measurement of weight using a bluetooth body weight scale	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight (in kg or pounds) at 12 weeks	Measurement of weight using a bluetooth body weight scale	Baseline, 12 weeks
Physical Activity and Sedentary Behavior	The Global Physical Activity Questionnaire (GPAQ) is a 16 item scale.	Baseline, 12 weeks
Dietary Intake	Diet ID is powered by Diet Quality Photo Navigation (DQPN®). It is a digital toolkit and 1 component will be used in the study: ID assessment.	Baseline, 12 weeks
Habit/Automaticity	The Self-Report Behavioral Automaticity Index (SRBAI) is a 4-item measure.	Baseline, 12 weeks
Hunger VAS (Visual Analogue Scale)	The Hunger VAS (Visual Analogue Scale) is a reliable measure for appetite research. The Hunger VAS asks "How hungry did you feel over the past week" and is composed of a line with words anchored at each end describing the extremes (Not at all hungry, Extremely hungry). Participants are asked to make a mark on the line corresponding to their feelings and quantification of the measurement is done by measuring the distance from the left end of the mark.	Baseline, 12 weeks
Impact on Quality of Life	The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) is a validated self-report measure for an individual's perception of how their weight affects their day-to-day life	Baseline, 12 weeks
Well-being	The World Health Organization (WHO-5) Well-being Index consists of five statements, which respondents rate, in relation to the past two weeks, using a six-point Likert scale	Baseline, 12 weeks
Body Appreciation	The Body Appreciation Scale (BAS-2) measures individuals acceptance of, favorable opinions toward, and respect for their bodies. There are 10 items, each assessed on a scale from 1-never to 5-always. Higher scores indicate higher body appreciation.	Baseline, 12 weeks
Self-Compassion	The Self-Compassion Scale (SCS) is a 26-item measure of self-compassion that is psychometrically valid and theoretically coherent. The SCS consists of six subscales: self-kindness, self-judgment, common humanity, isolation, mindfulness, and over-identified. Subscales are computed by calculating the mean of subscale item responses. A total self-compassion score can be obtained by reverse scoring the negative subscale items (self-judgment, isolation, and over-identification) and computing a grand mean of all six subscale means. Higher scores indicate greater self compassion.	Baseline, 12 weeks
Weight Bias	The Weight Bias Internalization Scale (WBIS-2F) has 13 items and responses are rated on a 7-point Likert scale(strongly disagree -strongly agree). Responses provide insight on the participant's internalized beliefs and feelings regarding their weight. There are two subscales: Weight-Related Distress (7 items; 7-13; Cronbach's alpha =0.910) and Weight-Related Self-Devaluation (6 items; 1-6; Cronbach's alpha =0.763). The WBIS-2F has been tested for validity in people with overweight and obesity and the two factor model demonstrated good to excellent fit with the data. Scores are calculated by taking an average of the response values. Questions 1,2,4,5, should be reverse scored before calculating the average. Higher scores indicating greater internalized weight bias.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: WW International Inc
• Investigators: Principal Investigator: Kara Marlatt, PhD, MPH, WW International Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2024
• Primary Completion (Actual): February 5, 2026
• Study Completion (Actual): February 5, 2026

Study Registration Dates

• First Submitted: September 18, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Alcohol Deterrents; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Narcotic Antagonists; Metformin; Naltrexone; Bupropion
• Other Study ID Numbers: GLP1 Transition Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes