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NCT Number: NCT07092618

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

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.

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Key information

Conditions

Longevity Aging GLP-1 Geroscience

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

AgelessRx

Chicago, Illinois, 60605, United States

Location status: Recruiting

Location contact

Ashley Valdes, BS

CONTACT

[email protected]

650-272-3169

Stefanie Morgan, PhD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

Primary outcomes

  1. 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

    Participant weight will be self-reported every 4 weeks and will be compared against baseline weight as percent departure from baseline.

    • Individuals that maintain the relative weight over the course of six months post-GLP-1 receptor agonist cessation
    • Individuals that have less weight gain over the course of six months post-GLP-1 receptor agonist cessation using the combinatorial therapies than those who do not

  2. 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

    Participant weight will be self-reported every 4 weeks and will be compared against baseline weight as percent departure from baseline.

  3. 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

    Participant weight will be self-reported every 4 weeks and will be compared against baseline weight as percent departure from baseline.

Secondary outcomes

  1. Evaluate the effectiveness of metformin on perceived metabolic health status in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

    Time frame: 6 months

    Perceived metabolic health status will be assessed by the ISQ standardized questionnaire

  2. Evaluate the effectiveness of metformin on biological metabolic health in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

    Time frame: 6 months

    Biological metabolic health will be assessed by a comprehensive metabolic blood panel, with each result reported in ng/dL and placed on a normalized scale identifying the upper and lower quartiles for healthy individuals

  3. Evaluate the effectiveness of metformin + rapamycin on perceived metabolic health status in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

    Time frame: 6 months

    Perceived metabolic health status will be assessed by the ISQ standardized questionnaire

  4. Evaluate the effectiveness of metformin + rapamycin on biological metabolic health in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

    Time frame: 6 months

    Biological metabolic health will be assessed by a comprehensive metabolic blood panel, with each result reported in ng/dL and placed on a normalized scale identifying the upper and lower quartiles for healthy individuals

  5. Evaluate the effectiveness of metformin + LDN on perceived metabolic health status in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

    Time frame: 6 months

    Perceived metabolic health status will be assessed by the ISQ standardized questionnaire

  6. Evaluate the effectiveness of metformin + LDN on biological metabolic health in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

    Time frame: 6 months

    Biological metabolic health will be assessed by a comprehensive metabolic blood panel, with each result reported in ng/dL and placed on a normalized scale identifying the upper and lower quartiles for healthy individuals

  7. Evaluate the effectiveness of metformin on mood-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Quality of life will be assessed by the PANAS standardized questionnaire

  8. Evaluate the effectiveness of metformin on physical health-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Quality of life will be assessed by the SF-36 standardized questionnaire

  9. Evaluate the effectiveness of metformin + rapamycin on mood-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Quality of life will be assessed by the PANAS standardized questionnaire

  10. Evaluate the effectiveness of metformin + rapamycin on physical health-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Quality of life will be assessed by the SF-36 standardized questionnaire

  11. Evaluate the effectiveness of metformin + LDN on mood-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Quality of life will be assessed by the PANAS standardized questionnaire

  12. Evaluate the effectiveness of metformin + LDN on physical health-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Quality of life will be assessed by the SF-36 standardized questionnaire

  13. Evaluate the effectiveness of metformin on tolerability of treatment in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Tolerability of treatment will be extrapolated from an extensive medical questionnaire sent to participants monthly and recorded throughout the trial

  14. Evaluate the effectiveness of metformin on long-term weight management practices in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Long-term weight management effectiveness will be assessed by reporting observed health changes as percent change in weight from baseline

  15. Evaluate the side effects of metformin in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Side effects will be monitored via an extensive medical questionnaire sent to participants monthly and recorded throughout the trial

  16. Evaluate the effectiveness of metformin + rapamycin on tolerability of treatment in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Tolerability of treatment will be extrapolated from an extensive medical questionnaire sent to participants monthly and recorded throughout the trial

  17. Evaluate the effectiveness of metformin + rapamycin on long-term weight management practices in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Long-term weight management effectiveness will be assessed by reporting observed health changes as percent change in weight from baseline

  18. Evaluate the side effects of metformin + rapamycin in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Side effects will be monitored via an extensive medical questionnaire sent to participants monthly and recorded throughout the trial

  19. Evaluate the effectiveness of metformin + LDN on tolerability of treatment in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Tolerability of treatment will be extrapolated from an extensive medical questionnaire sent to participants monthly and recorded throughout the trial

  20. Evaluate the effectiveness of metformin + LDN on long-term weight management practices in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Long-term weight management effectiveness will be assessed by reporting observed health changes as percent change in weight from baseline

  21. Evaluate the side effects of metformin + LDN in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent)

    Time frame: 6 months

    Side effects will be monitored via an extensive medical questionnaire sent to participants monthly and recorded throughout the trial

Study contacts

Contact information is provided by the study sponsor or research team.

James Watson, MD

CONTACT

[email protected]

(805) 497-8411

Sajad Zalzala, MD

CONTACT

[email protected]

(313) 355-8657

Sponsors and collaborators

Lead sponsor

AgelessRx

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jul 30, 2025
Registry last updated
Jul 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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