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

What this study is testing ClinicalTrials.gov NCT07092618 ↗

Description as written by the study sponsor.

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.

Treatments tested

• Metformin Drug

  Increasing doses from 500mg/d to 2000mg/d metformin

• Rapamycin Drug

  Increasing doses from 1mg/wk to 6mg/wk rapamycin

• Naltrexone Drug

  Increasing doses from 1.5mg b.i.d. to 4.5mg b.i.d. low-dose naltrexone

• Vitamin C Dietary supplement

  Placebo control - increasing doses from 250mg/d to 1000mg/d vitamin C (ascorbic acid)