PI: Jing Luo, MD, MPH
Funding Source: NIH/NIDDK
September 14, 2026 - June 30, 2029
Glucagon-like peptide-1 agonists (GLP-1 agonists) are now widely used to treat obesity, which affects more than 100 million Americans. Most available formulations require weekly injections and are expensive, and many patients discontinue or switch medications due to side effects or stockouts. Evidence from the STEP-4 and SURMOUNT-4 trials shows that abruptly stopping these medications often leads to rapid weight regain, yet more than half of people who start GLP-1 based therapy discontinue within a year despite this risk. There is an urgent need for evidence-based approaches to tapering or withdrawing these medications, often referred to as "off-ramping," as well as strategies to help patients maintain their weight loss during this transition.
This project, led by Principal Investigator Jing Luo, builds on prior work examining real-world GLP-1 outcomes, reasons for discontinuation across the UPMC health system, and clinician and patient perspectives gathered through a survey and patient engagement studio. The current study is a pilot trial that will randomly assign participants to one of three approaches after they have reached their target weight on a high-potency GLP-1 based therapy: continuing a maintenance dose, switching to a lower-dose alternate frequency regimen, or transitioning to a non-incretin based weight loss therapy. All three groups will also receive a home-based resistance exercise program and lifestyle counseling to support lean muscle mass. The study will assess the feasibility of recruiting and retaining participants, the acceptability of the alternative treatment strategies, and the feasibility of measuring weight change using data already collected in the electronic health record.
Findings from this pilot will lay the foundation for a future, fully powered multisite randomized trial, OFF-RAMP, that will test the effects of these three approaches on percent change in body weight at 12 months after randomization. Together, this work aims to give patients and clinicians the evidence they need to make informed decisions about stepping down GLP-1 based therapy while preserving long-term weight loss outcomes.