Aging, Obesity & Overweight
Conditions
Keywords
LinAge2, Biological Age, GLP-1 Receptor Agonist, Semaglutide, Tirzepatide, Weight Management Program, Lifestyle, Real-World Evidence, Cardiometabolic Biomarkers, Body Composition, Prospective Cohort
Brief summary
This study examines whether routine treatment with semaglutide or tirzepatide, prescribed with lifestyle coaching in a real-world weight-management program, is associated with changes in biological age measured by the LinAge2 clinical aging clock over 6 months.
Detailed description
This study will evaluate whether routine treatment with semaglutide or tirzepatide, prescribed in conjunction with lifestyle coaching support as part of standard-of-care in a real-world clinical weight-loss program, is associated with changes in biological age as measured by the LinAge2 clock. Aging is a primary driver of chronic disease, functional decline, and mortality. Obesity, through mechanisms such as mitochondrial dysfunction, oxidative stress, and chronic inflammation, may accelerate biological aging. Given that GLP-1 receptor agonists such as semaglutide and tirzepatide improve metabolic and cardiovascular health, this study will examine whether these benefits extend to biological aging as quantified by LinAge2, a clinical aging clock derived from standard clinical biomarkers. This is a six-month prospective observational cohort study involving approximately 440 adults aged 40-89 years who are overweight or obese and newly enrolled in the weight management program at NOVI Health (T3 Health PTE LTD), a private healthcare provider in Singapore. Clinical care and program delivery are provided by NOVI Health as part of routine practice. Participants will receive standard-of-care GLP-1 RA therapy (semaglutide or tirzepatide) together with personalized diet and physical activity interventions. Study procedures include baseline and six-month visits at the NOVI Health clinic, where anthropometry, body composition, blood and urine samples, questionnaires, and functional performance assessments will be conducted. Blood and urine samples will be collected by trained and certified nurses or phlebotomists, analyzed by an accredited external laboratory, and discarded thereafter; no biological materials will be stored. The National University of Singapore (NUS) research team provides scientific leadership in study design and conducts the development and application of the LinAge2 biological aging clock and analyses of de-identified data generated during routine clinical care at NOVI Health. NUS is not involved in participant recruitment, informed consent, clinical procedures, drug prescription, or biospecimen handling. The primary outcome is change in LinAge2 biological age from baseline to six months. Secondary outcomes include changes in body composition, cardiometabolic biomarkers, and functional clinical measures.
Interventions
Not applicable. This is an observational study.
Sponsors
National University of Singapore
T3 Health PTE LTD
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 40-89 years, who are newly enrolled in the NOVI OP+ weight management program. * BMI of ≥ 30 kg/m2 (obesity); OR * BMI of ≥ 27 kg/m2 to \< 30 kg/m2 (overweight) in the presence of at least one weight-related comorbid condition e.g. dysglycemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease.
Exclusion criteria
* Pregnancy or lactation. * Non-ambulatory status, total blindness, complete hearing loss, or inability to speak. * Medical history of, or self-reported, psychiatric illness, congenital or irreversible neurodegenerative diseases, cognitive impairment, or eating disorders that may affect adherence or assessment outcomes. * On GLP-1 RA, sulfonylurea or insulin medications for the past 3 months. * Active cancer on chemotherapy or immunotherapy. * Known hypersensitivity or contraindications to GLP-1 RAs. * Any condition, in the opinion of the attending clinician, that would jeopardize participant safety or interfere with study compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LinAge2 Biological Age | Baseline and 6 months | The primary outcome of this study is to determine the change in LinAge2 biological age estimates in response to the NOVI Health weight management program, which comprises GLP-1 RA therapy alongside personalized diet and physical activity interventions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Composition: Body Weight | Baseline and 6 months | Body weight measured in kilograms (kg); outcome is change from baseline to 6 months. |
| Change in Body Composition: Body Mass Index (BMI) | Baseline and 6 months | BMI calculated as weight (kg) divided by height (m²), reported in kg/m². |
| Change in Body Composition: Waist Circumference | Baseline and 6 months | Waist circumference measured in centimeters (cm) using a measuring tape |
| Change in Body Composition: Hip Circumference | Baseline and 6 months | Waist circumference measured in centimeters (cm) using a measuring tape |
| Change in Body Composition: Waist-to-Hip Ratio | Baseline and 6 months | Waist-to-hip ratio calculated as waist circumference / hip circumference |
| Change in Pulse Rate | Baseline and 6 months | Pulse rate measured in beats per minute (bpm) |
| Change in Blood Pressure | Baseline and 6 months | Systolic and Diastolic blood pressure measured in mmHg |
| Change in Body Composition: Body Fat Percentage | Baseline and 6 months | Body fat percentage (%) measured using a Tanita body composition analyzer (bioimpedance) |
| Change in Body Composition: Muscle Mass | Baseline and 6 months | Muscle mass measured in kilograms (kg) using a Tanita body composition analyzer (bioimpedance) |
| Change in Body Composition: Basal Metabolic Rate | Baseline and 6 months | Basal metabolic rate measured in kilocalories per day (kcal/day) as estimated by a Tanita body composition analyzer (bioimpedance) |
| Change in Body Composition: Metabolic Age | Baseline and 6 months | Metabolic age (years) estimated by a Tanita body composition analyzer (bioimpedance) |
| Change in Functional Clinical Measures: Handgrip Strength (Southampton protocol) | Baseline and 6 months | Handgrip strength measured using a handheld dynamometer following the Southampton protocol; reported in kilograms (kg) |
| Change in Functional Clinical Measures: Change in Chester Step Test Estimated VO₂max | Baseline and 6 months | Chester Step Test performed to estimate VO₂max, reported in mL/kg/min |
| Change in Functional Clinical Measures: Change in Five-Times Sit-to-Stand Test Time | Baseline and 6 months | Time to complete five sit-to-stand repetitions, reported in seconds |
| Change in Cardiometabolic: Glycohemoglobin (HbA1c) | Baseline and 6 months | Glycohemoglobin measured as percent (%) |
| Change in Cardiometabolic: Glucose | Baseline and 6 months | Glucose measured in mmol/L |
| Change in Cardiometabolic: Total Cholesterol | Baseline and 6 months | Total cholesterol measured in mmol/L |
| Change in Cardiometabolic: High-Density Lipoprotein (HDL) Cholesterol | Baseline and 6 months | HDL cholesterol measured in mmol/L |
| Change in Cardiometabolic: Triglycerides | Baseline and 6 months | Triglycerides measured in mmol/L |
| Change in Cardiometabolic: C-Reactive Protein (CRP) | Baseline and 6 months | C-reactive protein measured in mg/dL |
| Change in Hepatic: Alanine Aminotransferase (ALT) | Baseline and 6 months | ALT measured in U/L |
| Change in Hepatic: Aspartate Aminotransferase (AST) | Baseline and 6 months | AST measured in U/L |
| Change in Renal: Serum Creatinine | Baseline and 6 months | Creatinine measured in µmol/L |
| Change in Renal: Blood Urea Nitrogen | Baseline and 6 months | Blood urea nitrogen measured in mmol/L |
| Change in Renal: Urine Albumin | Baseline and 6 months | Urine albumin measured in mg/L |
| Questionnaire: PAR-Q Physical Activity Readiness Questionnaire | Baseline and 6 months | PAR-Q questionnaire (7 items). Reported as number of "Yes" responses (0-7) |
| Questionnaire: Smoking status | Baseline and 6 months | Self-reported smoking status assessed by questionnaire and categorized as current smoker, former smoker, or never smoker. |
| Questionnaire: Self-reported health | Baseline and 6 months | Question 1: General health condition. Self-rated general health assessed by a single questionnaire item with 5 response options (Excellent, Very good, Good, Fair, Poor). Question 2: Health compared with 1 year ago. Self-rated health compared with 1 year ago assessed by a single questionnaire item with response options (Better, About the same, Worse). |
| Questionnaire: Co-morbidity index (22 conditions) | Baseline | Number of self-reported comorbidities from a prespecified 22-condition (hypertension, diabetes mellitus, renal impairment, asthma, anemia, arthritis, coronary heart disease, angina, previous myocardial infarction, previous stroke, emphysema, thyroid disease, obesity, chronic bronchitis, liver disease, malignancy, osteoporosis, previous hip fracture, previous wrist fracture, previous spine fracture, cognitive impairment, and overnight hospitalization) |
| Questionnaire: Healthcare use index | Baseline | Self-reported number of healthcare visits in the past 12 months (count). From None to 13 times or more. |
Countries
Singapore
Contacts
CONTACTZhi Meng Lim, MSc
CONTACTHui Ching Michelle Lee, PhD
PRINCIPAL_INVESTIGATORJan Gruber, PhD
National University of Singapore
Outcome results
None listed