Evaluating Comparative Effectiveness of Glucose-lowering Therapy in People with HIV and Type 2 Diabetes

About This Grant

PROJECT SUMMARY In the era of modern antiretroviral therapy (ART), cardiometabolic diseases have become a leading cause of morbidity and mortality among people with HIV (PWH). Type 2 diabetes, a major contributor to cardiovascular and kidney disease, now affects approximately one in five PWH. PWH face unique metabolic challenges due to HIV infection and ART, including chronic inflammation and disrupted glucose and lipid metabolism. Despite these distinct metabolic derangements, population-specific evidence guiding the pharmacologic management of diabetes in PWH remains limited. This project seeks to generate real-world evidence addressing critical knowledge gaps on the comparative effectiveness of commonly used glucose-lowering agents—metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and sulfonylureas. The candidate is an internal medicine physician with a background in pharmacoepidemiology at Johns Hopkins University. During the award period, he will be mentored by a multidisciplinary team whose expertise spans diabetes and cardiometabolic comorbidities in PWH, machine learning, and causal inference methods. His long-term career goal is to become an independent clinician-investigator applying innovative machine learning and epidemiologic methods to improve clinical care for PWH with diabetes and other chronic conditions. The overarching objective of this project is to generate robust evidence to inform the pharmacologic management of type 2 diabetes among PWH. The proposed study will focus on three aims: (1) characterize the utilization of glucose-lowering therapies; (2) evaluate the comparative effectiveness of glucose-lowering therapies on glycemic control; and (3) estimate the effect of different glucose-lowering therapies on cardiovascular and renal outcomes and mortality among PWH with diabetes. This work will leverage the North American AIDS Cohort Collaboration on Research and Design (NA- ACCORD), a large, representative, multi-site cohort of over 190,000 people with HIV in the United States and Canada. Comparing glucose-lowering therapies on key clinical outcomes will generate population-specific evidence to inform clinical care for the growing population with HIV and diabetes. In parallel, the project will support the candidate’s development of the expertise needed to become an independent investigator capable of applying advanced quantitative methods to generate robust clinical evidence and improve the treatment of diabetes and other chronic conditions among PWH.