Overview
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.
Eligibility
Inclusion Criteria:
- Existing AgelessRx patient
- Adults (40 - 85 years of age)
- Any sex
- Any ethnicity
- BMI ≥ 22 kg/m^2
- Have been on GLP-1s (Wegovy, Ozempic, or a compounded form of GLP-1s) for at least three months before study initiation
- Have lost at least 15 lbs during their GLP-1 use
Exclusion Criteria:
- Individuals who are denied a longevity product by the AgelessRx medical team will not be asked to participate in any product specific test(s) or questionnaire(s)
- History of bariatric surgery
- Use of weight-loss medications other than GLP-1s within the past 6 months
- Age <40 years
- Contraindications to naltrexone, metformin, or rapamycin
- Significant psychiatric illness that may affect participation
- Pregnant or breastfeeding individuals