Over the past decade, clinical development and regulatory review of investigational drugs for diabetes and obesity have been guided by heightened standards for pre- and post-marketing assessment of cardiovascular safety. In high-risk patients with type 2 diabetes, several large multicentre cardiovascular outcome trials (CVOTs) have confirmed non-inferiority, i.e. cardiovascular safety for several glucose-lowering agents. More recent diabetes CVOTs have demonstrated major cardiovascular benefits for drugs representing two newer classes, sodium–glucose cotransporter (SGLT)-2 inhibition and glucagon-like peptide (GLP)-1 receptor agonists. Collectively, hard endpoint data from diabetes CVOTs have ushered in a new era of type 2 diabetes drug development and clinical care. Moreover, some unexpected cardiovascular side-effects have been unearthed for certain drugs.