Assessing Biological Aging in a Real-World Medical Weight Loss Program Using the LinAge2 Clinical Clock

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging; Obesity & Overweight
• Intervention / Treatment: Other: Not applicable. This is an observational study.

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.

• Study Type: Observational
• Enrollment (Estimated): 440

Contacts and Locations

• Study Contact: Name: Zhi Meng Lim, MSc; Phone Number: +65 90084510; Email: zmlim@nus.edu.sg
• Study Contact Backup: Name: Hui Ching Michelle Lee, PhD; Email: michelle.lee@novi-health.com

Study Locations

• Singapore
  • Singapore, Singapore, 119077
    • National University of Singapore
  • Singapore, Singapore, 068914
    • NOVI Health (T3 Health PTE LTD)
    • Contact: Hui Ching Michelle Lee, PhD; Phone Number: +65 82822765; Email: michelle.lee@novi-health.com
    • Sub-Investigator: Sue-Anne Ee Shiow Toh, MA MBBChir MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults aged 40-89 years who are overweight or obese and newly enrolled in the NOVI Health weight management program in Singapore. Participants are selected from routine clinical practice at the NOVI Health clinic.

Description

Inclusion Criteria:

• Adults aged 40-89 years, who are newly enrolled in the NOVI OP+ weight management program.
• BMI of ≥ 27.5 kg/m2 (if Asian) or 30 kg/m2 (if non-Asian); OR
• BMI of ≥ 23 kg/m2 (if Asian) / 25 (if non-Asian) kg/m2 in the presence of a weight-related chronic condition (e.g., diabetes, pre-diabetes, polycystic ovarian syndrome, hypertension, fatty liver, high cholesterol).

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.
• Concomitant anti-diabetic therapy.
• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NOVI Health weight management cohort; Adults newly enrolled in the NOVI Health weight management program receiving standard-of-care GLP-1 receptor agonist therapy (semaglutide or tirzepatide) and lifestyle coaching (diet and physical activity) as part of routine clinical care. Medication type is determined by routine clinical care and patient-clinician decision-making, not by the research study.	Other: Not applicable. This is an observational study.; Not applicable. This is an observational study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Composition: Body Weight	Body weight measured in kilograms (kg); outcome is change from baseline to 6 months.	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.	Baseline and 6 months
Change in Body Composition: Waist Circumference	Waist circumference measured in centimeters (cm) using a measuring tape	Baseline and 6 months
Change in Body Composition: Hip Circumference	Waist circumference measured in centimeters (cm) using a measuring tape	Baseline and 6 months
Change in Body Composition: Waist-to-Hip Ratio	Waist-to-hip ratio calculated as waist circumference / hip circumference	Baseline and 6 months
Change in Pulse Rate	Pulse rate measured in beats per minute (bpm)	Baseline and 6 months
Change in Blood Pressure	Systolic and Diastolic blood pressure measured in mmHg	Baseline and 6 months
Change in Body Composition: Body Fat Percentage	Body fat percentage (%) measured using a Tanita body composition analyzer (bioimpedance)	Baseline and 6 months
Change in Body Composition: Muscle Mass	Muscle mass measured in kilograms (kg) using a Tanita body composition analyzer (bioimpedance)	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)	Baseline and 6 months
Change in Body Composition: Metabolic Age	Metabolic age (years) estimated by a Tanita body composition analyzer (bioimpedance)	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)	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	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	Baseline and 6 months
Change in Cardiometabolic: Glycohemoglobin (HbA1c)	Glycohemoglobin measured as percent (%)	Baseline and 6 months
Change in Cardiometabolic: Glucose	Glucose measured in mmol/L	Baseline and 6 months
Change in Cardiometabolic: Total Cholesterol	Total cholesterol measured in mmol/L	Baseline and 6 months
Change in Cardiometabolic: High-Density Lipoprotein (HDL) Cholesterol	HDL cholesterol measured in mmol/L	Baseline and 6 months
Change in Cardiometabolic: Triglycerides	Triglycerides measured in mmol/L	Baseline and 6 months
Change in Cardiometabolic: C-Reactive Protein (CRP)	C-reactive protein measured in mg/dL	Baseline and 6 months
Change in Hepatic: Alanine Aminotransferase (ALT)	ALT measured in U/L	Baseline and 6 months
Change in Hepatic: Aspartate Aminotransferase (AST)	AST measured in U/L	Baseline and 6 months
Change in Renal: Serum Creatinine	Creatinine measured in µmol/L	Baseline and 6 months
Change in Renal: Blood Urea Nitrogen	Blood urea nitrogen measured in mmol/L	Baseline and 6 months
Change in Renal: Urine Albumin	Urine albumin measured in mg/L	Baseline and 6 months
Questionnaire: PAR-Q Physical Activity Readiness Questionnaire	PAR-Q questionnaire (7 items). Reported as number of "Yes" responses (0-7)	Baseline and 6 months
Questionnaire: Smoking status	Self-reported smoking status assessed by questionnaire and categorized as current smoker, former smoker, or never smoker.	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).	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)	Baseline
Questionnaire: Healthcare use index	Self-reported number of healthcare visits in the past 12 months (count). From None to 13 times or more.	Baseline

Collaborators and Investigators

• Sponsor: National University of Singapore
• Collaborators: T3 Health PTE LTD
• Investigators: Principal Investigator: Jan Gruber, PhD, National University of Singapore

Publications and helpful links

General Publications

• Fong S, Pabis K, Latumalea D, Dugersuren N, Unfried M, Tolwinski N, Kennedy B, Gruber J. Principal component-based clinical aging clocks identify signatures of healthy aging and targets for clinical intervention. Nat Aging. 2024 Aug;4(8):1137-1152. doi: 10.1038/s43587-024-00646-8. Epub 2024 Jun 19.

Helpful Links

• LinAge2 clinical aging clock

Study record dates

Study Major Dates

• Study Start (Estimated): February 2, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Semaglutide; Body Composition; Lifestyle; Tirzepatide; Weight Management Program; Real-World Evidence; Biological Age; Prospective Cohort; GLP-1 Receptor Agonist; Cardiometabolic Biomarkers; LinAge2
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: NUS-IRB-2025-845

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in publications will be shared upon reasonable request after primary publication. Requests will be reviewed by the study team and require a data use agreement. Data will be provided in de-identified form and will not include direct identifiers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No