Treating Painful Diabetic Peripheral Neuropathy: An Update

 


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Am Fam Physician. 2016 Aug 1;94(3):227-234.

  Patient information: See related handout on nerve pain in diabetes, written by the authors of this article.

Author disclosure: No relevant financial affiliations.

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.

Painful diabetic peripheral neuropathy (DPN) occurs in approximately 30% of patients with diabetes mellitus who are hospitalized and in 25% of patients with diabetes who are treated in the office setting.1 It develops as a late manifestation of uncontrolled or long-standing diabetes.1 As many as 12% of patients with painful DPN do not report symptoms, and 39% of patients with the disorder do not receive any treatment.2

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Pregabalin (Lyrica), gabapentin (Neurontin), amitriptyline (except in older adults), or duloxetine (Cymbalta) should be used as first-line treatment for painful diabetic peripheral neuropathy.

A

13, 8, 9, 22

The serotonin-norepinephrine reuptake inhibitors venlafaxine and desvenlafaxine (Pristiq) and opioid-like medications (tramadol and extended-release tapentadol [Nucynta ER]) may be considered if first-line medications do not provide adequate pain relief.

A

13, 6, 811

Lidocaine 5% patch, capsaicin 0.075% cream, isosorbide dinitrate spray, and transcutaneous electrical nerve stimulation can be added to therapy for painful diabetic peripheral neuropathy.

B

2, 8, 15, 27, 40


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Pregabalin (Lyrica), gabapentin (Neurontin), amitriptyline (except in older adults), or duloxetine (Cymbalta) should be used as first-line treatment for painful diabetic peripheral neuropathy.

A

13, 8, 9, 22

The serotonin-norepinephrine reuptake inhibitors venlafaxine and desvenlafaxine (Pristiq) and opioid-like medications (tramadol and extended-release tapentadol [Nucynta ER]) may be considered if first-line medications do not provide adequate pain relief.

A

13, 6, 811

Lidocaine 5% patch, capsaicin 0.075% cream, isosorbide dinitrate spray, and transcutaneous electrical nerve stimulation can be added to therapy for painful diabetic peripheral neuropathy.

B

2, 8, 15, 27, 40


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

Distal symmetric polyneuropathy, which is characterized by burning pain, paresthesias, and numbness that follows a stocking-glove pattern and progresses proximally, occurs in approximately 26% of patients with DPN. Less than 20% of patients with diabetes experience dynamic mechanical allodynia (pain in response to stroking lightly), thermal hyperalgesia (increased sensitivity to pain by thermal stimuli), or pain attacks.

Poorly controlled blood glucose levels, especially greater variation in glucose levels, contribute to the occurrence and severity of painful DPN.3 A 2012 Cochrane review of two randomized controlled trials (RCTs; n = 1,228) found that enhanced glucose control in patients with type 1 diabetes significantly reduced the risk of developing DPN (risk difference = 1.84%; 95% confidence interval [CI], −1.11 to −2.56). A similar analysis of four RCTs in patients with type 2 diabetes, however, did not show a statistically significant reduction in the rate of DPN with enhanced glucose control.4 Cardiovascular risk

The Authors

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MATTHEW J. SNYDER, DO, FAAFP, is associate program director of the Saint Louis University Family Medicine Residency Program in Belleville, Ill., which is affiliated with Scott Air Force Base....

LAWRENCE M. GIBBS, MD, FAAFP, is an assistant clinical professor in the Saint Louis University Family Medicine Residency Program, Belleville.

TAMMY J. LINDSAY, MD, FAAFP, is an associate clinical professor with the Department of Family and Community Medicine at Saint Louis University School of Medicine, St. Louis, Mo.

Author disclosure: No relevant financial affiliations.

Address correspondence to Matthew J. Snyder, DO, Saint Louis University, 180 S. Third St., Suite 400, Belleville, IL 62220 (e-mail: mdrnsnyder@gmail.com). Reprints are not available from the authors.

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