Pathogenetic treatments for diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (alpha-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.