Effectiveness of Microdosed GLP-1 in Improving Health, Quality of Life, and Longevity Measures

Participants will be assigned to one of three groups: 1) control, 2) microdosed sublingual semaglutide, 3) microdosed subcutaneous semaglutide. At baseline and every 4 weeks thereafter, participants will be asked to complete surveys on health, wellness, mood, demographic information, and similar. Additionally, at baseline and every 12 weeks thereafter, they will be requested to complete evaluative blood work to measure CBC, CMP, and standard health biomarker panels (e.g., cholesterol, glucose, creatinine, sodium, potassium). From baseline throughout the duration of the study, participants will be given the option to share data from wearable activity and health trackers with the research team for greater accuracy in evaluating measures of activity, sleep, heart rate, and similar.

• GLP-1 (Drug), also known as Semaglutide: Sublingual GLP1 (weekly), Subcutaneous GLP1 (weekly), Sublingual Placebo (weekly) for up to 6 months.
• Placebo (Drug): Sublingual Placebo (weekly) for up to 6 months

Primary outcomes

• Change in self-reported pain levels in participants microdosing GLP1s [6 months]: Participants will complete an extensive medical questionnaire every 4 weeks over a 24-week period to monitor self-reported pain levels
• Concentration of complete blood cells, as a measure of immunological health, in participants microdosing GLP1s [6 months]: CBC panel will be analyzed every 12 weeks over a 24-week period, reported in thousands of cells per microliter with the change from baseline reported as percent deviation and compared to normalized range of healthy individuals
• Concentration of basic metabolites (cholesterol, glucose, creatinine, sodium, potassium), as a measure of immunological health, in participants microdosing GLP1s [6 months]: BMP panel will be analyzed every 12 weeks over a 24-week period, reported in mg/dL with the change from baseline reported as percent deviation and compared to a normalized range of healthy individuals
• Change in mood in participants microdosing GLP1s [6 months]: Mood will be assessed every 4 weeks over a 24-week period using the SF-36 standardized questionnaire with deviation reported as percent change from baseline
• Change in heart rate variability in participants microdosing GLP1s [6 months]: Participants will wear health devices with data monitored every 4 weeks over a 24-week period to observe change in heart rate variability, being defined as the variability of a participant's resting heart rate. Variability will be measured as an average deviation from baseline heart rate at each timepoint and reported as percent difference.
• Changes in sleep patterns in participants microdosing GLP1s [6 months]: Wearable health device data will be monitored over the 24-week period assessing REM vs non-REM sleep and reported as a ratio
• Change in frequency of physical activity in participants microdosing GLP1s [6 months]: The change in frequency of physical activity, defined as a departure from baseline in time spent performing moderate to rigorous physical exercise, will be captured via wearable health device data and will be reported as percent difference from baseline in steps taken.
• Change in frequency of physical activity in participants microdosing GLP1s [6 months]: The change in frequency of physical activity, defined as a departure from baseline in time spent performing moderate to rigorous physical exercise, will be captured via wearable health device data and will be reported as percent difference from baseline in calories burned.

Secondary outcomes

• Variation in concentration of metabolic health biomarkers in participants microdosing GLP1s [6 months]: Changes in HbA1c levels will be assessed every 12 weeks and reported as a percent deviation from baseline
• Variation in concentration of metabolic health biomarkers in participants microdosing GLP1s [6 months]: Changes in LDL cholesterol levels will be assessed every 12 weeks and reported as a percent deviation from baseline
• Variation in concentration of metabolic health biomarkers in participants microdosing GLP1s [6 months]: Changes in HDL cholesterol levels will be assessed every 12 weeks and reported as a percent deviation from baseline
• Variation in concentration of metabolic health biomarkers in participants microdosing GLP1s [6 months]: Changes in triglyceride levels will be assessed every 12 weeks and reported as a percent deviation from baseline

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* New or existing AgelessRx patient
* Adults (aged 18-65)
* Any sex
* Any ethnicity
* BMI ≥ 20 kg/m\^2
* Interest in taking microdoses of semaglutide for health and longevity improvement with no intent to seek weight loss improvement.

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 other weight-loss medications currently or within the past 6 months
* Contraindications to semaglutide
* Significant psychiatric illness that may affect participation
* Pregnant or breastfeeding individuals

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• Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15. PMID 27633186
• Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018 Apr 3;27(4):740-756. doi: 10.1016/j.cmet.2018.03.001. PMID 29617641

• Informed Consent Form (PDF, 2024-08-28)