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LongevityPhase 2/3NCT07092618

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

A Phase 2/3 study testing Metformin, Rapamycin and Naltrexone in people with Longevity and GLP-1, run by AgelessRx at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 85 years
Conditions the study is for
Longevity, GLP-1, Geroscience
What is being tested?
Metformin, Rapamycin and Naltrexone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
1 siteUnited States
Study dates
17 Dec 2024to Aug 2025
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sajad Zalzala, MD contact

(313) 355-8657

doctor@agelessrx.com

James Watson, MD contact

(805) 497-8411

jpfaber@ircm.org

United States1 site, 1 recruiting
  • AgelessRx

    Chicago, Illinois, 60605

    Ashley Valdes, BS, 650-272-3169, avaldes@agelessrx.com

    Stefanie Morgan, PhD

    Recruiting

Other trials in United States

About this study

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

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:

Read more
  • 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.
Being tested
Metformin, Rapamycin, Naltrexone, Vitamin C
Keywords
Longevity, Aging, Healthy Aging, GLP-1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

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

  • RapamycinDrug

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

  • NaltrexoneDrug

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

  • Vitamin CDietary supplement

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

Study groups in NCT07092618
Study groupRoleWhat they receive
Metformin + LDNExperimentalMonth 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.
Receives: Drug: Metformin; Drug: Naltrexone
MetforminExperimentalMonth 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
Receives: Drug: Metformin
Metformin + RapamycinExperimentalMonth 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
Receives: Drug: Metformin; Drug: Rapamycin
Placebo (Vitamin C)Placebo comparatorMonth 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
Receives: Dietary Supplement: Vitamin C

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate the effectiveness of metformin in maintaining GLP1-induced weight loss in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

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

    1. Individuals that maintain the relative weight over the course of six months post-GLP-1 receptor agonist cessation
    2. 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

    Measured: 6 months

  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)

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

    Measured: 6 months

  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)

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

    Measured: 6 months

Secondary outcomes (21)
  1. Evaluate the effectiveness of metformin on perceived metabolic health status in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent)

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

    Measured: 6 months

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

    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

    Measured: 6 months

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

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

    Measured: 6 months

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

    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

    Measured: 6 months

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

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

    Measured: 6 months

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

    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

    Measured: 6 months

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

    Quality of life will be assessed by the PANAS standardized questionnaire

    Measured: 6 months

  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)

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

    Measured: 6 months

  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)

    Quality of life will be assessed by the PANAS standardized questionnaire

    Measured: 6 months

  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)

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

    Measured: 6 months

  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)

    Quality of life will be assessed by the PANAS standardized questionnaire

    Measured: 6 months

  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)

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

    Measured: 6 months

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

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

    Measured: 6 months

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

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

    Measured: 6 months

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

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

    Measured: 6 months

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

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

    Measured: 6 months

  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)

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

    Measured: 6 months

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

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

    Measured: 6 months

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

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

    Measured: 6 months

  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)

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

    Measured: 6 months

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

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

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2025
  2. Study start17 Dec 2024
  3. Primary completionAug 2025 (estimated)
  4. Study completionAug 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07092618
Sponsor's protocol ID
ALRx009
Status last verified
May 2025
First submitted
18 Dec 2024
Last updated
30 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Metformin, Rapamycin and Naltrexone in people with Longevity and GLP-1, run by AgelessRx at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sajad Zalzala, MD ((313) 355-8657, doctor@agelessrx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025; AzTrials last refreshed its copy on 8 Nov 2026.

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