Recruiting
Phase 2
Phase 3

Metformin, Rapamycin, Naltrexone

Sponsor:

AgelessRx

Code:

NCT07092618

Conditions

Longevity

GLP-1

Geroscience

Aging

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Interventions

Metformin

Rapamycin

Naltrexone

Vitamin C

Study Details

Brief 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

Study ID

NCT07092618

Start date

Dec 17, 2024

Status verified date

May, 2025

Completion date

Aug, 2025

Anticipated

Primary completion date

Aug, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

150 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Metformin + LDN

Month 1: 500mg/d MET, reduce Wegovy (or equivalent) to 1.7mg/wk or Ozempic (or equivalent) to 1.0mg/wk, add LDN 1.5mg b.i.d.

Month 2: Increase MET to 1000mg/d, reduce Wegovy (or equivalent) to 1.0mg/wk or Ozempic (or equivalent) to 0.5mg/wk, increase LDN to 3mg b.i.d.

Month 3: Increase MET to 1500mg/d, reduce Wegovy (or equivalent) to 0.5mg/wk or Ozempic (or equivalent) to 0.25mg/wk, increase LDN to 4.5mg b.i.d.

Months 4-12: increase MET to 2000mg/d, stop Wegovy (or equivalent) or Ozempic (or equivalent) entirely, continue LDN 4.5mg b.i.d.

experimental: Metformin

Month 1: 500mg/d MET, reduce Wegovy (or equivalent) to 1.7mg/wk or Ozempic (or equivalent) to 1.0mg/wk

Month 2: Increase MET to 1000mg/d, reduce Wegovy (or equivalent) to 1.0mg/wk or Ozempic (or equivalent) to 0.5mg/wk

Month 3: Increase MET to 1500mg/d, reduce Wegovy (or equivalent) to 0.5mg/wk or Ozempic (or equivalent) to 0.25mg/wk

Months 4-12: increase MET to 2000mg/d, stop Wegovy (or equivalent) or Ozempic (or equivalent) entirely

experimental: Metformin + Rapamycin

Month 1: 500mg/d MET, reduce Wegovy (or equivalent) to 1.7mg/wk or Ozempic (or equivalent) to 1.0mg/wk, add 1mg/wk rapamycin

Month 2: Increase MET to 1000mg/d, reduce Wegovy (or equivalent) to 1.0mg/wk or Ozempic (or equivalent) to 0.5mg/wk, increase rapamycin to 2mg/wk

Month 3: Increase MET to 1500mg/d, reduce Wegovy (or equivalent) to 0.5mg/wk or Ozempic (or equivalent) to 0.25mg/wk, increase rapamycin to 4mg/wk

Months 4-12: increase MET to 2000mg/d, stop Wegovy (or equivalent) or Ozempic (or equivalent) entirely, increase rapamycin to 6mg/wk

placebo comparator: Placebo (Vitamin C)

Month 1: 250mg/d Vitamin C, reduce Wegovy (or equivalent) to 1.7mg/wk or Ozempic (or equivalent) to 1.0mg/wk

Month 2: Increase Vitamin C to 500mg/d, reduce Wegovy (or equivalent) to 1.0mg/wk or Ozempic (or equivalent) to 0.5mg/wk

Month 3: Increase Vitamin C to 750mg/d, reduce Wegovy (or equivalent) to 0.5mg/wk or Ozempic (or equivalent) to 0.25mg/wk

Months 4-12: increase Vitamin C to 1000mg/d, stop Wegovy (or equivalent) or Ozempic (or equivalent) entirely

Interventions

Metformin

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

Rapamycin

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

Naltrexone

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

Vitamin C

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

Primary outcome measure

  • Evaluate the effectiveness of metformin in maintaining GLP1-induced weight loss in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent) [ Time Frame: 6 months ]
  • Evaluate the effectiveness of metformin + rapamycin in maintaining GLP1-induced weight loss in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) [ Time Frame: 6 months ]
  • Evaluate the effectiveness of metformin + LDN in maintaining GLP1-induced weight loss in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

Sajad Zalzala, MD

(313) 355-8657doctor@agelessrx.com

James Watson, MD

(805) 497-8411jpfaber@ircm.org

Locations

AgelessRx

Recruiting

Chicago, Illinois, United States, 60605

Contacts

Ashley Valdes, BS

650-272-3169avaldes@agelessrx.com

Principal Investigator:

Stefanie Morgan, PhD

More Information

Sponsor

AgelessRx

Last update posted

Jul 30, 2025

Last verified

May, 2025

Keywords

  • Longevity
  • Aging
  • Healthy Aging
  • GLP-1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AgelessRx on 2025-07-30.