A Diabetes Treatment Strategy to Reduce the Risk of Cardiovascular Events: Clinical Benefits and Potential of Linagliptin

Dipeptidyl peptidase-4 (DPP-4) inhibitors suppress degradation of active glucagon-like peptide-1 and promote insulin secretion from pancreatic β cells in a blood glucose-dependent manner to decrease the blood glucose level. They lower the risk of hypoglycemia without causing weight gain and may protect pancreatic β cells; thus, DPP-4 inhibitors may overcome the challenges faced by conventional diabetes treatments. In particular, linagliptin, which has been shown to prevent cardiovascular events in meta-analyses of randomized studies and phase III studies performed, might extend healthy life expectancy, which is the goal of diabetes treatment. Given that one goal of diabetes treatment is prevention of cardiovascular events, glycemic control alone does not suffice; thus, expectations are placed on DPP-4 inhibitors with more potent effects regarding cardiovascular events. In fact, the greatest risk factor for cardiovascular events in patients with diabetes is a high LDL cholesterol level, followed by a high triglyceride level and a low HDL cholesterol level. Thus, future DPP-4 inhibitors must serve to effectively control diabetes and eliminate other risk factors. In addition to its hypoglycemic effect, linagliptin suppresses hepatic steatosis and has beneficial effects on lipid metabolism. Because of these favorable properties, linagliptin may be ascribed as a second-generation DPP-4 inhibitor.