With over 25 million Americans affected and annual costs upwards of $174 billion, diabetes remains a national public health priority. While there are many effective medications for diabetes, non-adherence to these evidence-based therapies is extremely common and is a central contributor to poor diabetic outcomes. TARGIT-Diabetes is a randomized controlled trial enrolling 6,000 patients to evaluate whether targeting and tailoring telephone interventions based on patients’ predicted risk of non-adherence and their disease control will improve overall glycemic control and do so in a cost-efficient manner.