Understanding the cardiovascular risk with non-insulin antidiabetic drugs

Introduction: Diabetes mellitus is a major public health problem with significant macro- and microvascular complications. Achievement of glucose control is associated with a substantial reduction of microvascular events, while the effects of antidiabetic drugs in macro-vascular complications are less clear. This review summarizes and critically discusses the cardiovascular effects of non-insulin antidiabetic agents. Areas covered: A selective literature search of Pubmed was performed regarding the efficacy and safety of non-insulin antidiabetic agents in randomized controlled clinical trials and relevant meta-analyses. Data are presented for all major classes of antidiabetic drugs: metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 analogues, and SGLT-2 inhibitors. Efficacy and safety were focused on the cardiovascular system. Expert opinion: Disparities in cardiovascular safety and efficacy between antidiabetic drugs exist. Metformin remains the first-choice drug with proven cardiovascular benefits. The cardiovascular profile of sulfonylureas is yet unclarified, while thiazolidinediones seem to be effective in secondary stroke prevention but heart failure concerns limit their use. The cardiovascular safety of DPP-4 inhibitors has been demonstrated, without however significant morbidity and mortality benefits. SGLT-2 inhibitors and GLP-1 analogues offer significant cardiovascular benefits and are recommended for patients with overt cardiovascular disease.