Whither pathogenetic treatments for diabetic polyneuropathy?

Diabetes Metab Res Rev. 2013 Jul;29(5):327-33. doi: 10.1002/dmrr.2397.


Diabetic distal symmetric polyneuropathy (DSPN) occurs in around one-third of patients with diabetes and is associated with significant morbidity and increased mortality. Diagnosis and clinical assessment of DSPN remain a challenge, not only for the physician in clinical practice but also for clinical trials. Optimal diabetes control is generally considered an essential first step in the prevention and management of DSPN. However, glycaemic control alone may be insufficient to prevent the development or progression of DSPN, especially in type 2 diabetes. Near-normoglycaemia is also difficult to achieve in a significant proportion of patients. Although considerable advances have been made in symptomatic pain management, these have not addressed the problem of sensory deficits and have no impact on the underlying pathogenesis of DSPN. There remains a lack of treatment options that effectively target the natural history of the disease. Several pathogenetic treatment approaches have been investigated, but evidence from clinical trials is limited with a number of treatments having shown disappointing results. However, some pathogenetic therapies have shown clinically relevant improvements in neuropathic endpoints in randomised controlled trials, in particular α-lipoic acid and Actovegin. These advances in DSPN disease modification need to be confirmed with further robust evidence from clinical trials together with a better understanding of the mechanisms of action of promising treatments.

Keywords: diabetic peripheral neuropathy; glycaemic control; neuropathy diagnosis; pain management; pathogenetic treatment.

Publication types

  • Review

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors
  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / therapy
  • Diabetic Neuropathies / diagnosis
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / physiopathology
  • Diabetic Neuropathies / prevention & control
  • Disease Progression
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Hyperglycemia / prevention & control
  • Pain Management / trends
  • Polyneuropathies / diagnosis
  • Polyneuropathies / drug therapy*
  • Polyneuropathies / physiopathology
  • Polyneuropathies / prevention & control
  • Vasodilator Agents / therapeutic use


  • Enzyme Inhibitors
  • Vasodilator Agents
  • Aldehyde Reductase