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Diabetic Peripheral Neuropathy: Prevention and Treatment

This is a corrected version of the article that appeared in print.

Scott Bragg, PharmD
Sarah Tucker Marrison, MD, PhD
Sean Haley, MD, MPH

American Family Physician. 2024;109(3):226-232.

Author disclosure: No relevant financial relationships.

Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy.

Diabetic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 50% of patients with diabetes.1 It commonly presents as distal symmetric polyneuropathy with a stocking-and-glove distribution and a loss of sensation that may be painful or asymptomatic, starting in the toes and moving proximally. Diabetic peripheral neuropathy may result in a loss of protective sensation and cascade into the development of foot ulcers, wounds, infections, and tissue necrosis.2,3

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating Comments
Intensive glycemic control and lowering blood pressure are recommended to reduce the risk of developing diabetic peripheral neuropathy.7,8,11 [corrected] A Multiple high-quality studies support intensive glycemic management and control of metabolic diseases to improve patient-oriented outcomes
Duloxetine (Cymbalta) and pregabalin (Lyrica) are considered first-line therapy for patients with painful diabetic peripheral neuropathy.23,24,33,34 A Multiple high-quality studies support duloxetine and pregabalin; long-term safety of pregabalin warrants further research
Amitriptyline and gabapentin are alternative first-line treatments, but these options have more adverse effects than other first-line treatments.26,27,33,35 B Multiple low-quality, patient-oriented outcome studies support use; use caution in older adults and in those taking higher doses
Topical lidocaine and capsaicin are second-line treatment options, with less evidence of benefit but few safety concerns.20,45 B Limited-quality studies support use, but few serious adverse effects exist
Opioids and opioid/serotonin-norepinephrine reuptake inhibitor therapies (e.g., tramadol, tapentadol [available as brand Nucynta extended-release]) should be avoided because of serious adverse events and availability of other effective treatment options.6,20 C Multiple guidelines recommend against using opioids for patients with diabetic peripheral neuropathy

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 https://www.aafp.org/afpsort.

SCOTT BRAGG, PharmD, is an associate professor in the Department of Clinical Pharmacy and Outcomes Sciences and the Department of Family Medicine at the Medical University of South Carolina, Charleston.

SARAH TUCKER MARRISON, MD, PhD, is an assistant professor in the Department of Family Medicine at the Medical University of South Carolina.

SEAN HALEY, MD, MPH, is an assistant professor in the Department of Family Medicine at the Medical University of South Carolina.

Address correspondence to Scott Bragg, PharmD, Medical University of South Carolina, 173 Ashley Ave., MSC 140 Room CP240, Charleston, SC 29425 (braggsc@musc.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial relationships.

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