Novel therapeutics and targets for the treatment of diabetes

Abstract

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.

Keywords::

• β-cell
• diabetes
• therapy
• weight loss

Financial & competing interests disclosure

All authors are employees of Array BioPharma Inc. and are compensated by salary, stock options, and/or own the company’s stock. Array BioPharma Inc. has active research programs in clinical and preclinical discovery for the treatment of diabetes and its complications. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.