Aging, Geroscience, GLP-1, Longevity
Conditions
Keywords
Longevity, Aging, Healthy Aging, GLP-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.
Interventions
DRUGMetformin
Increasing doses from 500mg/d to 2000mg/d metformin
DRUGRapamycin
Increasing doses from 1mg/wk to 6mg/wk rapamycin
DRUGNaltrexone
Increasing doses from 1.5mg b.i.d. to 4.5mg b.i.d. low-dose naltrexone
DIETARY_SUPPLEMENTVitamin C
Placebo control - increasing doses from 250mg/d to 1000mg/d vitamin C (ascorbic acid)
Sponsors
AgelessRx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the effectiveness of metformin in maintaining GLP1-induced weight loss in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent) | 6 months | 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 |
| Evaluate the effectiveness of metformin + rapamycin in maintaining GLP1-induced weight loss in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Participant weight will be self-reported every 4 weeks and will be compared against baseline weight as percent departure from baseline. |
| Evaluate the effectiveness of metformin + LDN in maintaining GLP1-induced weight loss in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Participant weight will be self-reported every 4 weeks and will be compared against baseline weight as percent departure from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the effectiveness of metformin on biological metabolic health in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent) | 6 months | 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 |
| 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 | Perceived metabolic health status will be assessed by the ISQ standardized questionnaire |
| Evaluate the effectiveness of metformin + rapamycin on biological metabolic health in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent) | 6 months | 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 |
| 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 | Perceived metabolic health status will be assessed by the ISQ standardized questionnaire |
| Evaluate the effectiveness of metformin + LDN on biological metabolic health in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent) | 6 months | 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 |
| Evaluate the effectiveness of metformin on mood-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Quality of life will be assessed by the PANAS standardized questionnaire |
| Evaluate the effectiveness of metformin on physical health-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Quality of life will be assessed by the SF-36 standardized questionnaire |
| Evaluate the effectiveness of metformin + rapamycin on mood-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Quality of life will be assessed by the PANAS standardized questionnaire |
| 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) | 6 months | Quality of life will be assessed by the SF-36 standardized questionnaire |
| 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) | 6 months | Quality of life will be assessed by the SF-36 standardized questionnaire |
| Evaluate the effectiveness of metformin on long-term weight management practices in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Long-term weight management effectiveness will be assessed by reporting observed health changes as percent change in weight from baseline |
| Evaluate the side effects of metformin in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Side effects will be monitored via an extensive medical questionnaire sent to participants monthly and recorded throughout the trial |
| Evaluate the effectiveness of metformin + rapamycin on tolerability of treatment in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Tolerability of treatment will be extrapolated from an extensive medical questionnaire sent to participants monthly and recorded throughout the trial |
| Evaluate the effectiveness of metformin + rapamycin on long-term weight management practices in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Long-term weight management effectiveness will be assessed by reporting observed health changes as percent change in weight from baseline |
| Evaluate the side effects of metformin + rapamycin in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Side effects will be monitored via an extensive medical questionnaire sent to participants monthly and recorded throughout the trial |
| Evaluate the effectiveness of metformin + LDN on tolerability of treatment in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Tolerability of treatment will be extrapolated from an extensive medical questionnaire sent to participants monthly and recorded throughout the trial |
| Evaluate the effectiveness of metformin + LDN on long-term weight management practices in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Long-term weight management effectiveness will be assessed by reporting observed health changes as percent change in weight from baseline |
| Evaluate the side effects of metformin + LDN in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Side effects will be monitored via an extensive medical questionnaire sent to participants monthly and recorded throughout the trial |
| Evaluate the effectiveness of metformin on tolerability of treatment in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Tolerability of treatment will be extrapolated from an extensive medical questionnaire sent to participants monthly and recorded throughout the trial |
| Evaluate the effectiveness of metformin + LDN on mood-related quality of life in participants weaning off of Ozempic (or equivalent) or Wegovy (or equivalent) | 6 months | Quality of life will be assessed by the PANAS standardized questionnaire |
| Evaluate the effectiveness of metformin on perceived metabolic health status in participants weaning off of Ozempic or Wegovy (or compounded semaglutide equivalent) | 6 months | Perceived metabolic health status will be assessed by the ISQ standardized questionnaire |
Countries
United States
Contacts
Primary ContactSajad Zalzala, MD
Backup ContactJames Watson, MD
Outcome results
None listed