EPA interrupts multiple atherosclerotic and diabetes-related mechanisms caused by glucose. In the subpopulation of REDUCE-IT that had diabetes at baseline, treatment with IPE, which is converted to EPA by lipases in the intestinal lumen, experienced a 23% relative risk reduction in the primary endpoint. Elevated levels of glucose have been shown to increase the rate of oxidation in model membranes and induce formation of cholesterol liquid-crystalline domains. Due to its favourable orientation within the membrane and highly conjugated structure, EPA interrupts free radical propagation and cholesterol domain formation, thereby maintaining cholesterol distribution and preventing further acyl chain degradation. EPA-derived resolvin E1 has also been shown to reduce plasma glucose and insulin levels, a mechanism dependent on its receptor ERV1/ChemR23. Finally, EPA can bind to the free fatty acid receptor GPR120, which can increase GLUT4 translocation to the membrane and increase glucose uptake in adipocytes, as well as interrupt inflammatory signalling to NF-κB. COX2, cyclooxygenase-2; EPA, eicosapentaenoic acid; IPE, icosapent ethyl; RRR, relative risk reduction; RvE1, resolvin E1.