NCT07092618

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

Effectiveness of Alternative Therapies in Maintaining Weight Loss Achieved by GLP-1 Medications Post-Cessation: A Randomized, Controlled Trial

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: AgelessRx · Industry
• Sex: All
• Age: 40 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Longevity
• GLP-1
• Geroscience
• Aging

Interventions

Type	Name	Description
DRUG	Metformin	Increasing doses from 500mg/d to 2000mg/d metformin
DRUG	Rapamycin	Increasing doses from 1mg/wk to 6mg/wk rapamycin
DRUG	Naltrexone	Increasing doses from 1.5mg b.i.d. to 4.5mg b.i.d. low-dose naltrexone
DIETARY_SUPPLEMENT	Vitamin C	Placebo control - increasing doses from 250mg/d to 1000mg/d vitamin C (ascorbic acid)

Timeline

• Start date: 2024-12-17
• Primary completion: 2025-08-01
• Completion: 2025-08-01
• First posted: 2025-07-30
• Last updated: 2025-07-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study