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

NCT07092618 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ALRx009
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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

Keywords

Longevity; Aging; Healthy Aging; GLP-1

Outcome Measures

Primary Outcomes (3)

• 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

  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)

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

  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)

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

  6 months

Secondary Outcomes (21)

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

  6 months

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

  6 months

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

  6 months

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

  6 months

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

  6 months

Study Arms (4)

Metformin + LDN

EXPERIMENTAL

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.

Drug: Metformin; Drug: Naltrexone

Metformin

EXPERIMENTAL

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

Drug: Metformin

Metformin + Rapamycin

EXPERIMENTAL

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

Drug: Metformin; Drug: Rapamycin

Placebo (Vitamin C)

PLACEBO COMPARATOR

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

Dietary Supplement: Vitamin C

Interventions

Metformin DRUG

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

Metformin; Metformin + LDN; Metformin + Rapamycin

Rapamycin DRUG

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

Metformin + Rapamycin

Naltrexone DRUG

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

Metformin + LDN

Vitamin C DIETARY_SUPPLEMENT

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

Placebo (Vitamin C)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AgelessRx: lead

Study Sites (1)

AgelessRx

Chicago, Illinois, 60605, United States

RECRUITING

MeSH Terms

Interventions

Metformin; Sirolimus; Naltrexone; Ascorbic Acid

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Macrolides; Lactones; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Stefanie Morgan, PhD

  AgelessRx

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sajad Zalzala, MD

CONTACT

(313) 355-8657; doctor@agelessrx.com

James Watson, MD

CONTACT

(805) 497-8411; jpfaber@ircm.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: July 30, 2025
• Study Start: December 17, 2024
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Access Criteria: IPD will be shared with Institutional Review Board (IRB) approval or at the discretion of the PI/Sponsor

Locations

US (1)