Novel therapeutics and targets for the treatment of diabetes.

The microvascular complications of insufficiently controlled diabetes (neuropathy, retinopathy and nephropathy) and the marked increased risk of macrovascular events (e.g., stroke and myocardial infarction) have a dire impact on society in both human and economic terms. In Type 1 diabetes total β-cell loss occurs. In Type 2 diabetes, partial β-cell loss occurs before diagnosis, and the progressive β-cell loss during the life of the patient increases the severity of the disease. In patients with diabetes, increased insulin resistance in the muscle and liver are key pathophysiologic defects. In addition, defects in metabolic processes in the fat, GI tract, brain, pancreatic α-cells and kidney are detrimental to the overall health of the patient. This review addresses novel therapies for these deficiencies in clinical and preclinical evaluation, emphasizing their potential to address glucose homeostasis, β-cell mass and function, and the comorbidities of cardiovascular disease and obesity.