Critical review of oral drug treatments for diabetic neuropathic pain-clinical outcomes based on efficacy and safety data from placebo-controlled and direct comparative studies

Diabetes Metab Res Rev. May-Jun 2005;21(3):231-40. doi: 10.1002/dmrr.552.


The present review aims to evaluate the efficacy and safety of a selection of oral treatments for the management of painful diabetic neuropathy. A literature review was conducted retrieving placebo-controlled and direct comparative studies with a selection of oral treatments for painful diabetic neuropathy. All studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated as the percentage improvement in pain intensity between baseline and endpoint. Tolerability was evaluated by means of study discontinuations due to adverse events and by incidence of drug-related adverse events. The analyzed trials enrolled different patient populations with mostly small numbers of patients. The great variability in dosages and dose titration schemes, cross-over designs with variable wash-out periods, and other design schemes made comparison between the different studies difficult. Gabapentin, lamotrigine, tramadol, oxycodone, mexiletine, and acetyl-L-carnitine were the only treatments studied in large (at least 100 patients), placebo-controlled parallel group trials.It is concluded that standardization in design and reporting for comparison of treatments is needed. Validated questionnaires for evaluation of the efficacy and safety should be further developed. Based on the reviewed randomised controlled trials, gabapentin shows good efficacy, a favourable side-effect profile with lack of drug interactions and therefore it may be a first choice treatment in painful diabetic neuropathy, especially in the elderly. However, head to head trials of current treatments are lacking and therefore randomized controlled trials are required to address this issue.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Analgesics, Opioid / administration & dosage*
  • Anticonvulsants / administration & dosage*
  • Antidepressive Agents, Tricyclic / administration & dosage*
  • Antipsychotic Agents / administration & dosage
  • Controlled Clinical Trials as Topic
  • Diabetic Neuropathies / drug therapy*
  • Humans


  • Analgesics, Opioid
  • Anticonvulsants
  • Antidepressive Agents, Tricyclic
  • Antipsychotic Agents