Type 2 diabetes (T2DM) is a global pandemic with approximately 350 million patients worldwide, driven largely by increasing prevalence of obesity. Multiple options exist for treatment of the primary disease and the array of associated cardiovascular disorders. Nonetheless, the majority of patients do not reach recommended glycemic goals, and there is an urgent need for more efficacious, cost-effective and safe therapies. The regulatory hurdle for new drugs is sizable and challenged by the specific requirement for cardiovascular mortality study. Given the magnitude of the challenges, highly collaborative efforts involving academia, biotech, pharma, regulatory agencies, patient advocacy groups and other key stakeholders are required to identify and advance new therapies that are substantially differentiated from current disease management.