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

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.

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.