An associated Quintiles White Paper discussed the US Food and Drug Administration’s December 2008 Guidance for Industry entitled Diabetes Mellitus — Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes,which made assessment of cardiovascular safety a critical focus during the development of new antidiabetic therapies for Type 2 diabetes mellitus (T2DM). In January 2010, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) released a draft guideline entitled Guideline on Clinical Investigation of Medicinal Products in the Treatment of Diabetes Mellitus, referred to from here on as “the Guideline.” This White Paper provides a brief historical perspective on the evolution of the Guideline and reviews the section that addresses cardiovascular safety. It also compares and contrasts the guidance provided by these two regulatory agencies.