GLP-1 weight loss maintenance strategies compared: full dose, tapered dose, or phentermine/topiramate

Maintaining weight loss after successful initial therapy, particularly with GLP-1 receptor agonists, presents a significant challenge. Longitudinal studies indicate substantial weight regain, often exceeding 50% of lost weight within a year, following abrupt GLP-1 discontinuation. This regain underscores the critical need for effective long-term weight management strategies beyond continuous full-dose GLP-1 therapy. Exploring alternative or modified regimens, such as dose tapering or transitioning to non-GLP-1 agents like phentermine/topiramate, could offer viable solutions to sustain weight loss and improve patient outcomes in obesity management.

This randomized, 12-month study will enroll 60 adults with obesity who have achieved weight loss on a GLP-1 medication. Participants will be assigned to one of three groups: (1) continued full-strength GLP-1, (2) tapered GLP-1 to every other week, or (3) transition to phentermine/topiramate. The protocol includes three on-site visits (baseline, 6, and 12 months) for physical measures and blood collection for lab testing, supplemented by monthly phone calls. Participants will also receive counseling and instruction in a home-based resistance exercise regimen (e.g., sit-to-stand, mini-squats, calf raises) two to three times a week to help maintain muscle mass.

This study is designed to assess the feasibility and acceptability of different weight loss maintenance strategies, rather than reporting definitive efficacy findings at this stage. The primary goals are to determine the acceptability of the proposed treatment strategies among participants and to collect preliminary data on weight changes and medication tolerability over 12 months. Researchers will monitor how participants' weight evolves early on and throughout the study, alongside tracking adverse events to gauge tolerability across the three intervention arms. Furthermore, a key objective is to evaluate the feasibility of recruiting 60 participants for this pilot, which will inform the design and potential scale of a larger, follow-up study. Data collection will also encompass adherence to the prescribed home-based resistance exercise regimen, aiming to understand its impact on muscle mass maintenance. This comprehensive data collection will provide crucial insights into the practical implementation and participant experience with these novel maintenance approaches.

The study aims to determine the acceptability of GLP-1 tapering or transition to phentermine/topiramate for weight loss maintenance, collecting data on weight changes and tolerability over 12 months.