Historique des études cardiovasculaires : de l'UGDP… aux dernières études

An increasing number of cardiovascular outcome studies in type 2 diabetes are now available. Schematically, they aimed either at investigating the protective effect of intensifying glucose control on both microangiopathic and macroangiopathic complications, or at proving the cardiovascular safety and if possible the efficacy of one specific antidiabetic agent. The UGDP study suggested an increased coronary risk of first-generation sulfonylureas, which was not confirmed by the UKPDS. The latter landmark study emphasized the cardiovascular protection provided by metformin. The PROactive trial reported favourable results, but which were controverted, with pioglitazone. ACCORD, ADVANCE, and VADT were unable to demonstrate a reduction in major cardiovascular events with the intensification of blood glucose control, and suggested that a too strong intensification leading to hypoglycemia could increase the cardiovascular mortality. Recent studies have proven the cardiovascular safety of insulin glargine, lixisenatide and gliptins (non-inferiority vs. placebo), whereas they showed a significant reduction in major cardiovascular events with liraglutide and semaglutide, and a remarkable reduction in cardiovascular and all-cause mortality as well as in the risk of heart failure with empagliflozin. Several ongoing large prospective trials should provide answers to remaining important questions in a near future.