Comparing Different Medication Regimens to Maintaining Weight Loss Among Adults With Obesity Using GLP-1s

Conditions

• Cardiometabolic Health Indicators
• Obesity & Overweight

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• GLP-1 dose reduction — DRUG
  Participants in this intervention arm will receive a reduced GLP-1 dose compared to usual care.
• non-GLP weight loss medication — DRUG
  Participants in this intervention arm will be switched to a non-GLP weight loss medication.
• Maintenance of GLP-1 dose — DRUG
  Participants in this arm will maintain their high-potency GLP-1 dosage.
• Resistance exercise regimen — BEHAVIORAL
  All participants will be recommended to do a "low touch" home-based resistance exercise regimen. These strength exercises will include: sit-to-stand, mini-squats, calf raises, leg extension, wall press-up, bicep curls two to three times a week. If too easy for a particular subject, the study may recommend regular push ups, planks, lunges and/or add a resistance band.
• Lifestyle/nutrition counseling — BEHAVIORAL
  Participants will be provided with guideline concordant weight loss maintenance education and counseling (i.e., calorie restriction, amount and intensity of physical activity, self-monitoring of weight, and measuring portion sizes).

Study Details

The purpose of this research is to compare weight loss among 3 groups: 1. people who stay on a GLP-1 drug at full strength (Group 1) 2. people who have their dose tapered to every other week, meaning slowly decreasing the dose and frequency of the full prescription you are currently taking (Group 2) 3. people who go off their GLP-1 and instead take an alternative weight loss drug or combination of drugs called bupropion \& naltrexone. These are not GLP-1 medications. (Group 3) The investigators want to see if the second and third options are effective at weight loss maintenance. This study will include a total of 60 participants. Participants will be randomly assigned to one of the three study groups. The goals of this current study are to: 1. determine the acceptability of these proposed treatment strategies, 2. collect data about how people's weight changes early on and throughout the study and how well people tolerate the medications. 3. determine whether it is feasible to recruit for a larger, follow-up study. There are 3 on site visits: at the start, and then 6 and 12 months. The study team will do monthly phone calls in between those visits. At the visits on site visits the study team will do various physical measures and collect blood for lab testing and provide participants with counseling to help with weight loss. The study team will instruct participants in a home-based resistance exercise regimen to help maintain muscle mass. This will include exercises such as: sit-to-stand, mini-squats, calf raises, leg extension, wall press-up, bicep curls two to three times a week. If these exercises are deemed too easy, participants may choose to do regular push ups, planks, lunges and/or add a resistance band.

Key Dates

First listed

Sep 21, 2026

Start date

Nov 1, 2026

Status verified

Sep 2026

Primary completion

Apr 30, 2027

Completion

Sep 30, 2028

Study Design

Enrollment

60 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Usual care
  Maintenance of high-potency GLP-1 based therapy. Participants will continue their dose at enrollment for the entire duration of study follow-up. This is the current standard of care when the medication is covered and available.
• Experimental: Low dose, alternate frequency
  GLP-1 dose reduction to lower-dose, alternate frequency. Participants on semaglutide at enrollment will gradually reduce their dose from 2.4mg to 1.7mg to 1.0mg to 0.5mg once a week to 0.5mg every other week. Participants on tirzepatide at baseline will gradually reduce their dose from 15mg to 12.5mg to 10mg to 7.5mg to 5mg once a week to 5mg every other week. Dose reductions are scheduled every 4 weeks.
• Experimental: Non-incretin based therapy
  After gradually reducing GLP-1 therapy, participants will start bupropion with naltrexone. Participants will gradually reduce their semaglutide or tirzepatide dosage following the schedule of the "low dose, alternate frequency" arm until either semaglutide is 0.5mg once a week or tirzepatide is 5mg once a week. Participants will then start bupropion at 75mg twice a day (maintenance dose 150mg twice a day). Dosage for naltrexone would start at 25mg once a day, with an increase to 25mg twice per day if there is a favorable benefit/risk profile.

Primary Outcome Measure

Feasibility of recruitment and retention [ Time Frame: Completion of participation, up to 12 months. ]

Central Contacts

• Jing Luo, MD
  412-383-3559
  [email protected]

Locations (1)

Find similar trials in Pittsburgh, PA

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