Metformin, rapamycin, and low-dose naltrexone trial aims to sustain GLP-1 weight loss post-cessation

Maintaining weight loss after discontinuing GLP-1 receptor agonist medications is a significant challenge, with many patients experiencing substantial weight regain. Current long-term GLP-1 therapy can be cost-prohibitive and not always feasible for all individuals, creating a critical gap in sustainable weight management strategies. This trial investigates whether alternative, potentially more accessible and affordable therapies, such as metformin, rapamycin, and low-dose naltrexone, can effectively preserve the metabolic benefits and weight reduction achieved by GLP-1s, addressing a key unmet need in post-cessation care.

This randomized, controlled trial will compare four groups of patients gradually discontinuing GLP-1 receptor agonist use: 1) control (no alternative therapy), 2) metformin alone, 3) metformin + rapamycin, and 4) metformin + low-dose naltrexone. Participants will follow a provided dosing and administration protocol for their assigned intervention. Researchers will assess changes in the percentage of weight regain, key metabolic indicators (e.g., HbA1c, lipid profile), and quality of life via patient-reported outcomes (PROs) over six months post-cessation. Blood work (CBC, CMP, standard health biomarker panels) will be completed at baseline and every 16 weeks.