Management of painful diabetic peripheral neuropathy

Diabetic peripheral neuropathy is commonly defined by the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes.1,2 Up to 30% of patients with diabetic peripheral neuropathy are affected by neuropathic pain, which is commonly reported in the feet and known as painful diabetic peripheral neuropathy.3,4,5

Multifactorial management of painful diabetic peripheral neuropathy

A multifactorial treatment approach is often needed to manage painful diabetic peripheral neuropathy and may include glycemic control, management of metabolic syndrome components such as dyslipidemia or obesity, and neuropathic pain management with pharmacological and/or non-pharmacological treatments.6–8

With glycemic control, various studies have shown that7,9:

Management of metabolic syndrome may include addressing dyslipidemia, obesity, and hypertension.6–8 Lifestyle interventions such as implementation of healthy eating plans, increased physical activity, and reduction of sedentary behavior can play a key role in the management of metabolic syndrome.6,7

Neuropathic pain management may involve oral and/or topical pharmacological treatment options, and non-pharmacological therapies such as neuromodulatory techniques, and/or lifestyle interventions.5,6 Combination therapy with multiple pharmacological agents and/or non-pharmacological methods may also be used.5,6

Management of painful diabetic peripheral neuropathy requires a multidisciplinary approach combining coordinated care from specialists in neurology, endocrinology, podiatry, pain management, and primary care physicians.6,8,10

Several factors contribute to management choices for painful diabetic peripheral neuropathy, including comorbidities, contraindications or physical limitations, drug-drug interactions, potential for adverse events, patient education and preferences, and/or cost.6,8

Treatment landscape and guidelines for painful diabetic peripheral neuropathy

Currently available FDA-approved pharmacological treatments to manage neuropathic pain in patients with painful diabetic peripheral neuropathy are the oral drugs pregabalin,11 duloxetine,12 and tapentadol extended-release (ER),13 and one topical agent, the capsaicin 8% topical system.14,a

FDA-approved or cleared non-pharmacological treatments for painful diabetic peripheral neuropathy include several spinal cord stimulation devices15,16 and one magnetic peripheral nerve stimulation device.17,a

Medical devices may be FDA approved or cleared. FDA clearance for medical devices requires a shorter and less stringent regulatory process than FDA approval of pharmaceutical drugs.18,19

Several US expert groups have published guidelines for the management of painful diabetic neuropathy, including:

Recommendations may vary across expert groups and contain not only FDA-approved or cleared treatments for painful diabetic peripheral neuropathy, but also off-label treatment options such as gabapentin, serotonin and norepinephrine reuptake inhibitors (other than duloxetine), tricyclic antidepressants, sodium channel blockers, lidocaine patches and plasters, or transcutaneous electrical stimulation.5,6,20–22

Although tapentadol ER has a US indication for painful diabetic peripheral neuropathy,13 current guidelines from the ASPN, ADA, AACE, and AAN do not recommend opioids for the treatment of painful diabetic peripheral neuropathy due to the high risk of addiction and other complications.5,6,20–22

Emerging therapeutic options and US initiatives

Ongoing research is being conducted to investigate new therapeutic options to address painful diabetic peripheral neuropathy.16 Furthermore, US initiatives, such as the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium and the National Institute of Health (NIH) Helping to End Addiction Long-term (HEAL) Initiative, also seek to improve care for diabetic foot ulcers and pain management by supporting clinical research in these areas.23,24

Effective management of painful diabetic peripheral neuropathy requires a multidisciplinary and multifactorial approach. Understanding diabetic peripheral neuropathy, recognizing the symptoms, and ensuring timely diagnosis are critical steps to enhance patient outcomes.

Diagnosis

Footnotes

aInformation is current as of May 2025.

AACE, American Association of Clinical Endocrinologists; AAN, American Academy of Neurology; ADA, American Diabetes Association; ASPN, American Society of Pain and Neuroscience; FDA, Food and Drug Administration; US, United States of America.

N/A-05-25-0007 | June 2025