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Doctor, I have painful diabetic neuropathy. Which medications are the best for treating this condition?

There are four major classes of medications that have been shown to reduce pain due to diabetic neuropathy. You may need to try several different types of drugs before you find the one that works best for you.

What is the evidence?


Oral medications vs placebo

Medication Class

No. of studies

(no. people)

OutcomeConfidence in Evidence*

16 (3,550)

Small effectModerate
Sodium Channel Blockers5 (566)Medium effectModerate
Serotonin-Norepinephrine Reuptake Inhibitors9 (1,884)Small effectModerate
Serotonin-Norepinephrine Reuptake Inhibitors-Opioid4 (775)Medium effectModerate
Nabilone (synthetic cannabinoid)1 (26)Large effect**Moderate

*only medications supported by evidence with moderate or high confidence are reported in this Table

**results should be interpreted with caution because only supported by a single small study

What kind of study was this?

This is an update for a 2011 guideline on medications for treatment of painful diabetic neuropathy. The guideline provides recommendations to physicians that are supported by evidence from a systematic review.  A systematic review summarises all available studies on a health care intervention.

Who? This guideline is supported by evidence from 34 randomized controlled studies involving people who had painful diabetic neuropathy.

What? The included studies compared medications with placebo.




Five major drug classes for oral medications:

1) Gabapentinoids (e.g., gabapentin, pregabalin, mirogabalin)

2) Sodium Channel Blockers (e.g., lamotrigine, oxcarbazepine, valproic acid)

3) Serotonin-Norepinephrine Reuptake Inhibitors (e.g., duloxetine, venlafaxine, desvenlafaxine)

4) Serotonin-Norepinephrine Reuptake Inhibitors-Opioids (e.g., tapentadol, tramadol)

5) Tricyclic Antidepressants (e.g., amitriptyline)

Other oral and topical drugs were evaluated that are not listed here

Placebo: A pill/needle/lotion containing an inactive substance that has no effect on the outcome. Sometimes, it is referred to as a "sugar pill."

Why was this research done?

Nerve damage (neuropathy) due to exposure of nerves to high glucose levels is a common problem in people with diabetes. The most common part of the body affected by diabetic neuropathy are the feet (often called diabetic foot). Nerve damage can cause pain, numbness, and reduced function. Treating pain due to diabetic neuropathy can be challenging, and completely eliminating the pain is rare. The reviewers wanted to know which drugs have the best evidence for reducing pain due to diabetic neuropathy. They found several different classes of drugs that reduced pain by at least a small amount. Each drug also has potential side effects that were not reviewed in this summary. Finding the right drug may require trying one drug for up to 12 weeks before switching to another one, if the first one either doesn't reduce pain, or the side effects are too difficult to tolerate. Failure of one drug to work, even within the same drug class, does not necessarily mean other drugs won't work.

This Evidence Summary is based on the following article:

Price R, Smith D, Franklin G, et al. Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary: Report of the AAN Guideline Subcommittee. Neurology. 2022 Jan 4;98(1):31-43. doi: 10.1212/WNL.0000000000013038. PubMed

Published: Tuesday, March 22, 2022

Please note that the information contained herein is not to be interpreted as an alternative to medical advice from a professional healthcare provider. If you have any questions about any medical matter, you should consult your professional healthcare providers, and should never delay seeking medical advice, disregard medical advice or discontinue medication based on information provided here.