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

AgelessRx

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Aging; Geroscience; Longevity; GLP-1

Treatments: Drug: Rapamycin; Drug: Metformin; Drug: Naltrexone; Dietary Supplement: Vitamin C

Study type: Interventional

Funder types: Industry

Identifiers

NCT07092618

ALRx009

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 4 patient groups, including a placebo group

Metformin + LDN

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone

Drug: Metformin

Metformin

Experimental group

Description:

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

Treatment:

Drug: Metformin

Metformin + Rapamycin

Experimental group

Description:

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

Treatment:

Drug: Metformin

Drug: Rapamycin

Placebo (Vitamin C)

Placebo Comparator group

Description:

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

Treatment:

Dietary Supplement: Vitamin C