Clinical Research Directory

Inclusion Criteria: * Adult male or non-pregnant female volunteers (Age 18-79) * Not currently taking more than two home oral antidiabetic agents, with or without a diagnosis of type 2 diabetes * Able and willing to stop home oral antidiabetic medications for 5 days prior to the start of the study, with approval from healthcare providers * Able and willing to give informed consent Exclusion Criteria: * Known contraindication for orforglipron (e.g., Personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2 (MEN 2), allergies to any component) * Personal history of pancreatitis, gallbladder disease, intestinal malabsorption, severe gastroparesis, gastric outlet obstruction, or other clinically significant gastrointestinal motility disorder * History of liver disease or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 x upper limit of normal * Estimated glomerular filtration rate (eGFR) \< 45 mg/min/1.73m2 per the Modification of Diet in Renal Disease equation * Active gallbladder disease or cholecystectomy within the past 6 months * Current use of a strong CYP3A4 inducer (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, rifabutin, or St. John's wort) or ritonavir, cobicistat, cyclosporine, or another strong CYP3A4 inhibitor that also inhibits OATP1B * Current simvastatin dose \>20 mg daily * Measured most recent HbA1c level greater than 7.5% in the last 6 months * Average glucose by fingerstick or continuous glucose monitor exceeding 180 mg/dL in the last 3 months * Current uses of any oral or injectable GLP-1 receptor agonists, insulin, or the use of two or more antidiabetic agents * Currently taking or planning to start other medication known to affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones during the study * Planned to change any prescribed medication during the study * Planned surgeries or procedures requiring general anesthesia during or within 10 days after completing the study * Participating in any other interventional study simultaneously * Dietary restrictions that prevent the consumption of the standardized liquid mixed meal * Pregnant, nursing, or postpartum in the last 6 months * Current suicidal ideation or suicide attempt within the past 5 years * Psychiatric illness, substance use disorder, or eating disorder that, in the opinion of the investigator, would compromise participant safety or study compliance