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

NCT ID: NCT07092618

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-17
• Study Completion Date: 2025-08-31

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 Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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

Naltrexone

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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

Rapamycin

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Vitamin C

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Metformin

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

Intervention Type: DRUG

Rapamycin

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

Intervention Type: DRUG

Naltrexone

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

Intervention Type: DRUG

Vitamin C

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

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AgelessRx

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefanie Morgan, PhD

Role: PRINCIPAL_INVESTIGATOR

AgelessRx

Locations

AgelessRx

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sajad Zalzala, MD

Role: CONTACT

doctor@agelessrx.com

(313) 355-8657

James Watson, MD

Role: CONTACT

jpfaber@ircm.org

(805) 497-8411

Facility Contacts

Ashley Valdes, BS

Role: primary

avaldes@agelessrx.com

650-272-3169

Other Identifiers

ALRx009

Identifier Type: -

Identifier Source: org_study_id