Clinical Research Directory

Inclusion Criteria: * Male or female, aged 50 to 80 years, inclusive. * Generally healthy, as determined by medical history and screening assessments, with no more than 2 stable, well-controlled chronic conditions. * Body-mass index (BMI) ≥25 kg/m². * No diagnosis of Type 1 or Type 2 diabetes mellitus and screening HbA1c \<6.5%. * Willing and able to provide written informed consent prior to any study-related procedures. * Willing and able to comply with all study procedures, including daily use of a compatible smartphone or tablet for app-based digital biomarker data collection and completion of required home study procedures. * If female and of childbearing potential, must be postmenopausal for at least one year. Exclusion Criteria: Metabolic \& Endocrine * Diagnosis of Type 1 or Type 2 diabetes mellitus, or HbA1c ≥6.5% at screening. * History of pancreatitis, medullary thyroid carcinoma (personal or family), or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). * History of significant or recurrent hypoglycemia requiring medical intervention. * Known Child-Pugh Class B or C hepatic disease. * BMI \<25 kg/m². Renal \& Genitourinary * Impaired renal function, defined as an estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m² at screening, or a reported renal problem. * History of diabetic ketoacidosis (DKA). * History of recurrent (≥3 in the last 12 months) or severe urinary tract infections or genital mycotic infections. Gastrointestinal * Self-reported history of severe gastrointestinal disease such as gastroparesis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), or chronic malabsorption syndromes; known gallstones; significant hypertriglyceridemia (e.g., triglycerides \>500 mg/dL); or prior biliary tract surgery. * Previous bariatric surgery that may affect drug absorption (e.g., gastric bypass). Cardiovascular * New York Heart Association (NYHA) Class III or IV congestive heart failure. * History of myocardial infarction, unstable angina, or stroke within the 6 months prior to screening. * Symptomatic hypotension or a screening systolic blood pressure consistently \<100 mmHg. Other Medical Conditions * Active malignancy within the last 2 years, with the exception of successfully treated non-melanoma skin cancer or cervical carcinoma in situ. * Known significant active liver disease (e.g., active hepatitis or cirrhosis), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times the upper limit of normal at screening. * History of lactic acidosis. * Any condition associated with an increased risk of lactic acidosis, such as severe dehydration or acute systemic illness at the time of screening. * Current or recent (within 2 years) diagnosis of anorexia nervosa, bulimia, or another eating disorder. * Current use of known nephrotoxic agents (e.g., high-dose NSAIDs or contrast agents) that may exacerbate renal risk. Concomitant Medications \& Lifestyle * Current use of any other glucose-lowering agents (e.g., insulin, other GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas). * Chronic use of systemic corticosteroids or loop diuretics. Inhaled or topical corticosteroids and stable replacement doses (e.g., hydrocortisone \<20 mg/day) are acceptable. * Participation in another interventional clinical trial within the 3 months prior to screening. * Excessive alcohol consumption, defined as more than 14 standard drinks per week for men or 7 per week for women, or a history of alcohol use disorder. * Known allergy or hypersensitivity to metformin, semaglutide, any SGLT-2 inhibitor, or any of their components or excipients. General * Any condition which, in the opinion of the investigator, would place the participant at undue risk or interfere with the study's conduct or the interpretation of its results. * Cognitive or mental impairment that would prevent the participant from understanding the consent form, adhering to daily tasks, or providing reliable data.