Beyond insulin replacement: addressing the additional needs of the diabetes patient

The management of type 2 diabetes mellitus (T2DM) typically focuses on correcting dysglycaemia to reduce risk for microvascular and macrovascular complications, possibly by reducing glucose-mediated oxidative stress. However, other cardiometabolic risk factors, including abdominal obesity and dyslipidaemia are often overlooked in the quest for perfect glucose control. The currently used antidiabetic agents, including insulin, metformin, sulphonylureas and thiazolidinediones, have limited efficacy on these risk factors. A number of new therapeutic agents are undergoing clinical development, including glucagon-like peptide 1 mimetics (exenatide and liraglutide) and dipeptidyl peptidase 4 inhibitors (sitagliptin and vildagliptin), which target the incretin system, and the cannabinoid-1 receptor antagonists (rimonabant), which target the endocannabinoid system, may hold some promise for meeting these unmet needs. In this review, the clinical properties of these agents and potential treatment pathways to best use these agents are discussed for improving the management of T2DM and cardiovascular risk.