Medications, Topicals, and Devices: Current Treatments for Diabetic Peripheral Neuropathy

By Jill Waldbieser

Diabetic peripheral neuropathy (DPN) affects millions of Americans and presents a unique therapeutic challenge. And because DPN is a progressive disease with no cure, symptoms—including pain—generally persist once they occur.

Pain caused by DPN presents differently in each individual. Often, DPN pain is severe enough to affect sleep and quality of life, and it has been tied to depression, anxiety, and other consequences.

Innovative new approaches for DPN are being studied, but current treatments include oral medications, topical treatments, and devices.

Oral medications

Pharmaceutical options include anticonvulsants such as pregabalin and gabapentin, which are often prescribed for nerve pain (the former has been FDA approved to specifically treat DPN pain). Also included in first-line treatments are antidepressants—especially those that act to inhibit the reuptake of serotonin and noradrenaline, such as duloxetine, which also has been FDA approved for DPN pain.

Unfortunately, according to Kwo Wei David Ho, MD, PhD, a neurologist and pain medicine specialist at the Nerve and Pain Institute in Tigard, Oregon, when a patient comes to see him, they’ve often tried multiple medications without success.

The challenging nature of treating DPN pain has led to some doctors prescribing opioids for the condition. However, there is a lack of evidence supporting their efficacy in treating DPN pain long-term, and risks associated with the use of these agents in people with diabetes, including addiction and death, says Rodica Pop-Busui, MD, PhD, a diabetologist, professor of internal medicine, metabolism, endocrinology, and diabetes, and vice chair of clinical research in the Department of Internal Medicine at the University of Michigan.

Pop-Busui also points out that even the most effective pain medications can have unpleasant side effects at the doses needed to reach pain reduction—lethargy, vertigo, constipation, and nausea which is why for many individuals with diabetes, a plan combining more than one agent or treatment option is needed.

Regular monitoring of diabetes and its potential complications is vital: “These complications are very quiet,” Armstrong explains. “You can have a serious problem about which you’re not aware.”

Topical treatments

Several topical treatments (applied as creams, gels, or patches) are used to treat diabetic neuropathic pain.

One is lidocaine, a local anesthetic that blocks the signals from nerve endings, creating a numbing sensation. This is often applied as a patch of up to 5% strength and works by restricting sodium ions from permeating the cells of neurons, affecting their charge and interrupting pain signals.

Another is a capsaicin 8% topical system, which is FDA approved for DPN pain. This prescription treatment, only available through an in-office visit, works to stimulate pain receptors so that they are less sensitive to neuropathic pain signals. Patients visit the doctor every few months for the treatment, during which an adhesive patch is applied for a half hour.

“Before [capsaicin 8%] was available, I dreaded having patients say they were experiencing [DPN] pain—we didn’t have a lot of options,” says Gary Graf, ARNP, an endocrinology specialist with the Cotton O’Neil Diabetes and Endocrinology Center in Topeka, Kansas. “Now, with this treatment, we have good success stories of patients with pain as bad as 7, 8, 9, or 10, going down to a 4 or lower.”

Graf notes that insurance companies often only approve the prescription topical treatment after one or two other DPN treatments have been tried unsuccessfully.


Another treatment for DPN is spinal cord stimulation. This treatment option is more invasive, involving an implanted device in the spine that works to block pain signals from traveling to the brain.

Having been used for years to treat pain from multiple conditions, spinal cord stimulation was FDA approved for the treatment of DPN in 2021 and has shown “quite a bit of success in clinical trials, averaging 70% to 80% of pain relief in refractory DPN cases,” Ho says.

As a test, a clinician injects a thin wire into the patient’s back, placed so it can stimulate the nerves and drown out pain. These small wires are connected to an external battery for about a week so the patient can see how it would help in their day-to-day life. The test has minimal risk and can be done safely in an office setting with or without sedation.

If the patient experiences pain relief during the trial, a permanent implanted stimulator is placed through a minor surgery.

“Not every patient needs it, but doctors should know about it as a potential option,” Ho says. “In some individuals, it can be life-changing.”

Peripheral nerve stimulation and dorsal root ganglion stimulation function similarly, but work to more specifically target the body’s peripheral nerves such as those in the feet, which are most affected by DPN. However, Ho notes, more research is needed to determine these treatments’ effectiveness for treating DPN.

Alternative therapies and lifestyle changes

Lifestyle changes are another option to help manage diabetes and DPN pain.

While it may seem counterintuitive, exercise can help alleviate pain from DPN, Pop-Busui says. It doesn’t have to be strenuous—simply walking makes a difference. Researchers believe exercise can help reduce neuropathic pain by potentially restoring some nerve function, increasing blood flow, and improving muscle function. Food choices, including supplements, may also affect this pain.

Acupuncture and transcutaneous electrical nerve stimulation (TENS) units have also been used to treat DPN. TENS units are over-the-counter devices that act similarly to spinal cord stimulators, but on an external and less powerful scale.

Ultimately, these treatments need more rigorous research to support their use, and scientists must keep searching for more options to treat DPN. In many cases, even after combining multiple treatments, individuals living with this condition still experience considerable pain.

“Significant breakthroughs in the treatment of painful diabetic polyneuropathy have emerged in the past decade,” Ho says. “However, awareness and understanding of these therapies remain limited among both medical professionals and the general public. While continued research is essential, urgent efforts to educate about these effective treatments are also imperative.”