Weight Loss Maintenance

This study is a single-site, pilot randomized factorial trial designed to evaluate the feasibility, acceptability, participant perceptions and preliminary effects of a multi-component behavioral intervention to support weight loss maintenance following discontinuation of GLP-1 and other anti-obesity medications. The intervention includes a standardized 10-week foundational weight loss maintenance program combined with candidate support components, including medically tailored meals, YMCA membership, and a structured mind-based program. Participants will be randomized using a 2 × 2 × 2 factorial design and followed for six months. Findings from this pilot study will inform optimization of a scalable intervention for future clinical trials.

This is a randomized controlled trial to compare the effect of AI-assisted multi-domain lifestyle and continued tirzepatide on body weight loss maintenance. The study consists of two phases: a 20-week lead-in phase, during which all participants will receive weekly subcutaneous tirzepatide at the maximum tolerated dose (MTD), followed by a 52-week intervention phase. Participants who meet the randomization criteria after the lead-in phase will be randomly assigned to either AI-assisted multi-domain lifestyle intervention or tirzepatide 5 mg

The purpose of this study is to find out what combination of components, if any, offers the best support for keeping weight off after someone loses weight. Long term weight loss maintenance is a challenge for many people who lose weight. There are many strategies, or components, people may use to avoid regain, but investigators do not know if there is a best, or optimal, combination of such components that can be done without adding a lot of cost or other burdens for people. * The primary goal of this clinical trial is to identify the optimal package that maximizes weight loss maintenance. * The study also wants to understand the reasons why these components may work and if certain components help specific sub-groups of people. Participants will engage in a 16-week Phase 1 Weight Loss Program. Participants who lose 5% or more of their weight during that program will continue to Phase 2 Extended Care and be randomly assigned to 0, 1, 2, 3, or all of four methods of weight loss maintenance. They will use their assigned package for 12 months. Researchers will compare 16 different possible combinations of components and learn which of the 16 packages offers the best support for keeping weight off. The four components participants could be assigned to in Phase 2 are: 1. Reduced Food Variety: Limiting the variety of foods participants eat by having them choose a few high-calorie, low nutrient foods to eat regularly 2. Home-based Resistance Training: Engaging in exercises that build strength from the comfort of the participant's own home 3. Buddy Training and Support: Having a friend or "buddy" get trained to support the participant 4. Acceptance and Commitment (ACT) Workshops: Having participants learn skills to handle tough thoughts and feelings about weight control in a healthy way Participants will have their weight measured and complete surveys 4 times if they complete both Phase 1 and Phase 2. During Phase 1, participants will attend weekly group sessions and be in touch with a study staff member investigators call a Wellness Coach. During Phase 2, participants will stay in touch with their Wellness Coach, use their assigned package, and answer questions about their experience periodically.

The TWIST 2.0 Study is a 12-month, 2-arm RCT in adults with recent weight loss. We will examine the efficacy of TRE on weight (Aim 1a) and fat mass (Aim 1b) regain, and describe changes in subjective appetite following a mixed-meal tolerance test (Exploratory).