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.
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.
Study Type
OBSERVATIONAL
Enrollment
440
Not applicable. This is an observational study.
NOVI Health (T3 Health PTE LTD)
Singapore, Singapore
National University of Singapore
Singapore, Singapore
LinAge2 Biological Age
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.
Time frame: Baseline and 6 months
Change in Body Composition: Body Weight
Body weight measured in kilograms (kg); outcome is change from baseline to 6 months.
Time frame: Baseline and 6 months
Change in Body Composition: Body Mass Index (BMI)
BMI calculated as weight (kg) divided by height (m²), reported in kg/m².
Time frame: Baseline and 6 months
Change in Body Composition: Waist Circumference
Waist circumference measured in centimeters (cm) using a measuring tape
Time frame: Baseline and 6 months
Change in Body Composition: Hip Circumference
Waist circumference measured in centimeters (cm) using a measuring tape
Time frame: Baseline and 6 months
Change in Body Composition: Waist-to-Hip Ratio
Waist-to-hip ratio calculated as waist circumference / hip circumference
Time frame: Baseline and 6 months
Change in Pulse Rate
Pulse rate measured in beats per minute (bpm)
Time frame: Baseline and 6 months
Change in Blood Pressure
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Systolic and Diastolic blood pressure measured in mmHg
Time frame: Baseline and 6 months
Change in Body Composition: Body Fat Percentage
Body fat percentage (%) measured using a Tanita body composition analyzer (bioimpedance)
Time frame: Baseline and 6 months
Change in Body Composition: Muscle Mass
Muscle mass measured in kilograms (kg) using a Tanita body composition analyzer (bioimpedance)
Time frame: Baseline and 6 months
Change in Body Composition: Basal Metabolic Rate
Basal metabolic rate measured in kilocalories per day (kcal/day) as estimated by a Tanita body composition analyzer (bioimpedance)
Time frame: Baseline and 6 months
Change in Body Composition: Metabolic Age
Metabolic age (years) estimated by a Tanita body composition analyzer (bioimpedance)
Time frame: Baseline and 6 months
Change in Functional Clinical Measures: Handgrip Strength (Southampton protocol)
Handgrip strength measured using a handheld dynamometer following the Southampton protocol; reported in kilograms (kg)
Time frame: Baseline and 6 months
Change in Functional Clinical Measures: Change in Chester Step Test Estimated VO₂max
Chester Step Test performed to estimate VO₂max, reported in mL/kg/min
Time frame: Baseline and 6 months
Change in Functional Clinical Measures: Change in Five-Times Sit-to-Stand Test Time
Time to complete five sit-to-stand repetitions, reported in seconds
Time frame: Baseline and 6 months
Change in Cardiometabolic: Glycohemoglobin (HbA1c)
Glycohemoglobin measured as percent (%)
Time frame: Baseline and 6 months
Change in Cardiometabolic: Glucose
Glucose measured in mmol/L
Time frame: Baseline and 6 months
Change in Cardiometabolic: Total Cholesterol
Total cholesterol measured in mmol/L
Time frame: Baseline and 6 months
Change in Cardiometabolic: High-Density Lipoprotein (HDL) Cholesterol
HDL cholesterol measured in mmol/L
Time frame: Baseline and 6 months
Change in Cardiometabolic: Triglycerides
Triglycerides measured in mmol/L
Time frame: Baseline and 6 months
Change in Cardiometabolic: C-Reactive Protein (CRP)
C-reactive protein measured in mg/dL
Time frame: Baseline and 6 months
Change in Hepatic: Alanine Aminotransferase (ALT)
ALT measured in U/L
Time frame: Baseline and 6 months
Change in Hepatic: Aspartate Aminotransferase (AST)
AST measured in U/L
Time frame: Baseline and 6 months
Change in Renal: Serum Creatinine
Creatinine measured in µmol/L
Time frame: Baseline and 6 months
Change in Renal: Blood Urea Nitrogen
Blood urea nitrogen measured in mmol/L
Time frame: Baseline and 6 months
Change in Renal: Urine Albumin
Urine albumin measured in mg/L
Time frame: Baseline and 6 months
Questionnaire: PAR-Q Physical Activity Readiness Questionnaire
PAR-Q questionnaire (7 items). Reported as number of "Yes" responses (0-7)
Time frame: Baseline and 6 months
Questionnaire: Smoking status
Self-reported smoking status assessed by questionnaire and categorized as current smoker, former smoker, or never smoker.
Time frame: Baseline and 6 months
Questionnaire: Self-reported health
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).
Time frame: Baseline and 6 months
Questionnaire: Co-morbidity index (22 conditions)
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)
Time frame: Baseline
Questionnaire: Healthcare use index
Self-reported number of healthcare visits in the past 12 months (count). From None to 13 times or more.
Time frame: Baseline