PROJECT SUMMARY/ABSTRACT Jung-Im Shin, MD, PhD, is an Assistant Scientist in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. She seeks a K01 Mentored Research Scientist Development Award in order to obtain essential skills and mentored research experience for an independent career as a research scientist in the field of pharmacoepidemiology and diabetes. The research proposal details a five-year plan consisting of in-depth training in novel causal inference methods, mentorship by Dr. Morgan Grams, MD, PhD, and Dr. Elizabeth Selvin, PhD, MPH, and pharmacoepidemiologic research in utilization, effectiveness, and safety of second-line therapy in patients with type 2 diabetes. The specific aims of the research agenda are to: 1) Describe the real-world epidemiology of second-line therapy among people with diabetes after metformin monotherapy; 2) Evaluate real-world effectiveness of 5 classes of second-line therapy for hyperglycemia management among similar people with diabetes after metformin monotherapy; and 3) Evaluate real-world risks of adverse events and benefits on long-term clinical outcomes of 5 classes of second- line therapy among similar people with diabetes after metformin monotherapy. Immediate career goals include the mastery of applying target trial emulation and estimating the effect of a dynamic treatment regime with Robin’s g-methods through an academic curriculum integrated with the research plan. Long-term, Dr. Shin aims to lead independent research programs investigating optimal treatment and decision-making to improve health outcomes of patients with type 2 diabetes. Completion of the proposed aims will provide vital information relevant to the approximately thirty million U.S. patients with type 2 diabetes. Type 2 diabetes is associated with high levels of morbidity and mortality. Although consensus exists around first-line therapy, there remains great uncertainty regarding the optimal choice of a second-line therapy, with inconsistent recommendations across guidelines. A better understanding of the risks and benefits of different classes of second-line antidiabetic drugs would greatly help clinical practice in patients with type 2 diabetes.