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

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 phentermine \& topiramate. 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 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, and bicep curls two to three times a week. If these exercises are deemed too easy, participants may choose to do regular pushups, planks, lunges and/or add a resistance band.

Participant Inclusion Criteria: * Aged 18 years or older. * Able to provide informed consent. * Pre-treatment diagnosis of obesity (BMI≥30kg/m2). * On a high potency GLP-1 based therapy (defined as semaglutide ≥1.7 mg or tirzepatide≥10mg). * Has achieved, or are close to achieving, a "target body weight." Target body weight will be defined by each individual patient through self-report or their treating clinician but should generally be at least 5% below their weight prior to first starting GLP-1 based therapy. * Has been on an incretin-based weight loss therapy for at least 6 months. Participant Exclusion Criteria: * Diagnosis of type 2 diabetes or pre-existing cardiovascular disease. * Pregnancy or nursing or are seeking to become pregnant in the next year. * Have had bariatric surgery. * Unwilling to reduce the dose of their GLP-1 medication for weight loss, or who are unwilling to switch to another non-GLP-1based weight loss medication. * Contraindications to phentermine: pre-existing cardiac arrhythmias, primary pulmonary hypertension, serious cardiac valvular disease, CAD, CVA, CHF, uncontrolled hypertension. * Contraindications to bupropion/naltrexone: chronic opioid use, seizure disorders, use of other bupropion containing products, uncontrolled hypertension, monoamine oxidase inhibitors. * Hyperthyroidism. * Glaucoma, or at risk for glaucoma. * History of substance use disorder. * History of suicidal ideation. * Concomitant monoamine oxidase inhibitors within 14 days. * Use of lithium. * Use of metformin.