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We used electronic medical record (EMR) data in the National Patient-Centered Clinical Research Network (PCORnet) to characterize “real-world” prescription patterns of Type 2 diabetes (T2D) medications. We identified a retrospective cohort of 613,203 adult patients with T2D from 33 datamarts (median patient number: 12,711) from 2012 through 2017 using a validated computable phenotype. We characterized outpatient T2D prescriptions for each patient in the 90 days before and after cohort entry, as well as demographics, comorbidities, non-T2D prescriptions, and clinical and laboratory variables in the 730 days prior to cohort entry. Approximately half of the individuals in the cohort were females and 20% Black. Hypertension (60.3%) and hyperlipidemia (50.5%) were highly prevalent. Most patients were prescribed either a single T2D drug class (42.2%) or had no evidence of a T2D prescription in the EMR (42.4%). A smaller percentage was prescribed multiple T2D drug types (15.4%). Among patients prescribed a single T2D drug type, metformin was the most common (42.6%), followed by insulin (18.2%) and sulfonylureas (13.9%). Newer classes represented approximately 13% of single T2D drug type prescriptions (dipeptidyl peptidase-4 inhibitors [6.6%], glucagon-like peptide-1 receptor agonists [2.5%], thiazolidinediones [2.0%], and sodium-glucose cotransporter-2 inhibitors [1.6%]). Among patients prescribed multiple T2D drug types, the most common combination was metformin and sulfonylureas (63.5%). Metformin-based regimens were highly prevalent in PCORnet's T2D population, whereas newer agents were prescribed less frequently. PCORnet is a novel source for the potential conduct of observational studies among patients with T2D. [ABSTRACT FROM AUTHOR]