Treating Painful Diabetic Peripheral Neuropathy: An Update

Am Fam Physician. 2016 Aug 1;94(3):227-34.


Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.

Publication types

  • Review

MeSH terms

  • Administration, Topical
  • Amines / therapeutic use
  • Amitriptyline / therapeutic use
  • Analgesics / therapeutic use*
  • Analgesics, Opioid / therapeutic use
  • Anesthetics, Local / therapeutic use*
  • Capsaicin / therapeutic use
  • Cyclohexanecarboxylic Acids / therapeutic use
  • Diabetic Neuropathies / therapy*
  • Duloxetine Hydrochloride / therapeutic use
  • Gabapentin
  • Humans
  • Isosorbide Dinitrate / therapeutic use
  • Lidocaine / therapeutic use
  • Phenols / therapeutic use
  • Pregabalin / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sensory System Agents / therapeutic use
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Tapentadol
  • Tramadol / therapeutic use
  • Transcutaneous Electric Nerve Stimulation*
  • Vasodilator Agents / therapeutic use
  • Venlafaxine Hydrochloride / therapeutic use
  • gamma-Aminobutyric Acid / therapeutic use


  • Amines
  • Analgesics
  • Analgesics, Opioid
  • Anesthetics, Local
  • Cyclohexanecarboxylic Acids
  • Phenols
  • Sensory System Agents
  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Vasodilator Agents
  • Amitriptyline
  • Tramadol
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Venlafaxine Hydrochloride
  • Duloxetine Hydrochloride
  • Lidocaine
  • Tapentadol
  • Isosorbide Dinitrate
  • Capsaicin