State-of-the-art pharmacotherapy for diabetic neuropathy.

The global epidemic of diabetes has led to an epidemic of diabetes complications. Diabetic neuropathy is the most common microvascular complication, of which diabetic peripheral neuropathy (DPN) and autonomic neuropathy (AN) are the most prevalent, affecting ~50% of patients. DPN results in pain with a poor quality of life and a loss of sensation with an increased risk of foot ulceration. Autonomic neuropathy can cause significant morbidity in a minority and is associated with increased mortality. The cornerstone of treatment to prevent or limit the progression of DPN/AN is multifactorial risk factor modification including treatment of glycemia, lipids and blood pressure. Whilst, there are no FDA-approved disease-modifying therapies, there are a number of therapies to relieve symptoms in DPN and AN. The authors discuss current approved therapies for painful diabetic neuropathy and autonomic neuropathy. They also address the potential role of improving risk factors to limit the development and progression of diabetic neuropathy and new pathogenetic and pain-relieving treatments. The FDA-approved Pregabalin and Duloxetine over 25 years ago and Tapentadol, 6 years ago for painful diabetic neuropathy. There are currently no FDA-approved disease-modifying treatments for diabetic neuropathy which has been attributed to inappropriate models of the disease with limited translational capacity and major limitations of trial designs and endpoints in clinical trials.