Effectiveness of Alternative Therapies in Maintaining Weight Loss Achieved by GLP-1 Medications Post-Cessation

Study Summary

The goal of this randomized, controlled trial is to evaluate the effectiveness of alternative therapies (metformin alone, with rapamycin, and with low-dose naltrexone) in maintaining weight loss in patients weaning off GLP-1 medications. The main questions it aims to answer are: * Whether the combination of metformin, with or without rapamycin or low-dose naltrexone, will be adequate to maintain the relative weight of individuals gradually discontinuing GLP-1 receptor agonist use. * Whether individuals discontinuing GLP-1 receptor agonist use who instead use a combination of metformin, with or without rapamycin or low-dose naltrexone, will experience less weight regain over the course of six months post-cessation than those who do not use any alternative medications. Researchers will compare the four groups: 1) control, 2) metformin, 3) metformin + rapamycin, and 4) metformin + low-dose naltrexone, to assess changes in the percentage of weight regain, metabolic indicators (e.g., HbA1c, lipid profile), and quality of life PROs, six months after cessation of GLP-1 therapy. Participants will: * Administer the assigned intervention following a dosing and administration protocol provided by the study and medical team. * Complete a medical intake for overall health status, medical history and demographic information, * Complete patient-reported outcomes/surveys and assessments * Complete blood work at baseline and every 16 weeks thereafter to measure CBC, CMP, and standard health biomarker panels (e.g., cholesterol, glucose, creatinine, sodium, potassium). * Share data from health wearables with the research team throughout the study to improve the accuracy of evaluating activity, sleep, heart rate, and other related healthspan measures.

Primary Outcome

Participant weight will be self-reported every 4 weeks and will be compared against baseline weight as percent departure from baseline. 1. Individuals that maintain the relative weight over the course of six months post-GLP-1 receptor agonist cessation 2. Individuals that have less weight gain over the course of six months post-GLP-1 receptor agonist cessation using the combinatorial therapies than those who do not

Conditions Studied

Interventions

• DRUG Metformin
• DRUG Rapamycin
• DRUG Naltrexone
• DIETARY_SUPPLEMENT Vitamin C

Study Locations (1)