The overarching aims of the DIRECT consortium, consisting of 20 leading academic groups in diabetes and 5 EFPIA companies, are to identify biomarkers that address current bottlenecks in diabetes drug development and to develop a stratified medicines approach to treatment of type 2 diabetes with either existing or novel therapies.There is heterogeneity in who develops diabetes, the rate at which their subsequent diabetes progresses, how they respond to diabetes therapy and who develops micro- and macrovascular complications. In the DIRECT consortium we propose to identify biomarkers to identify subtypes with rapid diabetes development and progression and altered response to diabetes treatments, and develop and use these biomarkers in clinical trials.Two phenotyping work packages will focus on glycaemic deterioration and therapeutic response. For each, the DIRECT consortium brings considerable existing resource, which will be augmented by large-scale prospective cohort collection with intensive physiological and imaging phenotyping. Additional data will be added, such as existing studies on acute response to intravenous beta-cell secretagogues, and functional genomics on human islets, liver, muscle and adipose tissue, to maximise the power and utility of an innovative integrated biology approach. To enable computational multi-level integration across phenotypes and data types, a robust and secure data repository will be developed with strict data governance. As the ultimate aim of DIRECT is patient stratification, biomarkers arising from the discovery work will be used to design one or more prospective clinical trials. These will validate the biomarker(s) of interest, and establish utility in clinical practice and/or trial design and drug development. As a result, this consortium offers considerable potential to achieve major progress towards a personalized medicines approach to the treatment of type 2 diabetes.