Cardiovascular role of novel antidiabetics in randomized controlled trials and newer recommendations
Pécsi Tudományegyetem, I. sz. Belgyógyászati Klinika, Endokrinológiai és Anyagcsere Tanszék, Pécs
For 10 years after the promising secondary prophylactic effect of a thiazolidinedione, pioglitazone, studies testing (i) strict glycemic control (ACCORD, ADVANCE, VADT), (ii) early glycemic control (NAVIGATOR, ORIGIN), (iii) agents acting on the incretin axis ( SAVOR-TIMI 53, EXAMINE, TECOS, ELIXA) or (iv) another thiazolidinedione, rosiglitazone (RECORD) became frustrating. However, EMPA-REG OUTCOME with empagliflozin, a member of the SGLT2 inhibitor group, has been a real breakthrough in respect of marked reduction (35-44%) of cardiovascular mortality, hospitalization for cardiac failure and hard nephropathic endpoints. Subsequently, the following antidiabetic drugs have been shown to have significant cardiovascular benefit: (i) two GLP-1R agonists, the liraglutide and semaglutide (LEADER and SUSTAIN-6), as well as (ii) pioglitazone (IRIS), this time clearly, and (iii) another SGLT2 inhibitor, canagliflozin (CANVAS). Where the different guidelines for type 2 diabetes are consistent are the usage of metformin as the first line drug (despite the lack of modern evidence) and the preference of SGLT2 inhibitors, even in the early stages.