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

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.

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

Conditions5

Interventions3

Locations1 site

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