Incretin-based therapies (dipeptidyl peptidase-4 inhibitor and glucagon like peptide-1 receptor agonists) have shown several potential CV beneficial effects in addition to glucose lowering, these including weigh reduction, decrease blood pressure, improvement of dyslipidemia and CV biomarkers, etc. Nevertheless, the long-term cardiovascular outcome trials (CVOT) for first 4 reported Incretin-based drugs (3 DPP4-i and 1 GLP-1 RA), the SAVOR-TIMI53, EXAMINE, TECOS and ELIXA, all showed the non-inferiority for major adverse cardiovascular event (MACE) compare to the standard of treatment. Moreover, a slightly increase of heart failure risk was observed in the SAVOR-TIMI trial, which aroused the worry in clinical Incretin-based therapy for the CV safety.
　　More recently, the LEADER and SUSTAIN 6 trials reported in 2016 have revealed the GLP-1 liraglutide and its long-acting form semaglutide, showing not only CV safety but CV benefits. In a median follow-up of 3.8 years of LEADER trail, the primary outcome occurred in significantly fewer patients in the liraglutide group (13.0%) than in the placebo group (14.9%) (hazard ratio〔HR〕, 0.87; 95% confidence interval〔CI〕, 0.78 to 0.97). In a follow-up approximately 2 years of the SUSTAIN6 trail, the MACE occurred in the semaglutide group and the placebo group was 6.6% and 8.9%. It also showed a superiority in CV protection (HR 0.74; 95% CI 0.58 to 0.95). We will review the detail and examine the findings relative to CV safety and efficacy.