Type 2 diabetes (T2D) is a major cause of death due to vascular complications. Thus, it is crucial that people with T2D receive optimal therapy already at diagnosis to optimize metabolic control, including glycemia and body weight, and minimize risk of complications. Response to therapy is heterogenous. ~30% of people with T2D do not respond well or tolerate first-line therapy, metformin, leading to sustained hyperglycaemia and intolerance. Many people with T2D may benefit from earlier and more targeted treatment with other drugs, i.e., GLP1RA, GLP1RA/GIPRA, SGLT2i, DPP4i or sulfonylureas. No biomarkers have been approved for predicting response or tolerance to T2D therapies. EPIPREDIA will tackle this unmet need using our unique expertise in epigenetics, clinical medicine and epidemiology together with exclusive cohorts. We will use prospective cohorts and innovative methods to discover and validate blood-based biomarkers predicting glycaemic response, tolerance and weight-change to T2D drugs in newly diagnosed patients with T2D. We will also study the impact of T2D drugs on their target cells. Finally, we plan to develop a clinically useful product for personalised T2D medicine. It will help patients receive optimal therapy, improving cardiovascular protection, reducing mortality and cost for society.