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

Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age40-85
SponsorAgelessRx

About this 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:

* 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Existing AgelessRx patient

Adults (40 - 85 years of age)

Any sex

Any ethnicity

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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)

Treatment groups

150 Participants
are divided into 4 treatment groups
Group A: Metformin + LDNExperimental treatment 2 interventions
Group B: MetforminExperimental treatment 1 intervention
Group C: Metformin + RapamycinExperimental treatment 2 interventions
Group D: Placebo (Vitamin C)Placebo comparator 1 intervention

Trial outcomes

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)

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

Time frame
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.

Time frame
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.

Time frame
6 months

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)

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

Time frame
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

Time frame
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

Time frame
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

Time frame
6 months

Other outcomes

Sponsors and contacts

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