Approved drugs for diabetic neuropathy better than placebo, review finds

In addition to approved drugs duloxetine, pregabalin, and tapentadol, some benefits were found with venlafaxine, oxcarbazepine, tricyclic antidepressants, tramadol, and botulinum toxin.


For reducing pain from diabetic peripheral neuropathy, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids (tapentadol, tramadol), and botulinum toxin were more effective than placebo, a systematic review found.

To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy on pain and quality of life, researchers reviewed the literature for reviews and studies on oral and topical analgesics that were published from Jan. 1, 2013, to May 24, 2016.

Although the most recent review had been published in 2014, some newer pharmacologic agents have come out since then, and the previous review did not synthesize evidence on patient-reported outcomes such as health-related quality of life, the authors wrote. The latest review considered 57 previously eligible studies, and added 24 more published studies and 25 unpublished studies from ClinicalTrials.gov. The randomized controlled trials that met eligibility compared 21 medications in 10,639 patients (range, n=20 to 804).

Results appeared online March 24 at Neurology.

The anticonvulsants pregabalin and oxcarbazepine (low strength of evidence), the serotonin and norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate strength of evidence), the drug classes of tricyclic antidepressants (low strength of evidence) and atypical opioids (low strength of evidence), and botulinum toxin (low strength of evidence) were all more effective than placebo. Typical opioids were not found to be effective for pain treatment of diabetic peripheral neuropathy. While most effect sizes were moderate or large, those for pregabalin and oxcarbazepine were small. The researchers noted that, while pregabalin has a similar mechanism of action to gabapentin and the agents are often used interchangeably, both the previous and updated reviews found that gabapentin was not more effective than placebo.

Researchers did not draw conclusions for any head-to-head drug comparisons because of insufficient evidence. Also, strength of evidence was insufficient for many comparisons because there were few studies for many agents. Reporting bias was a particular concern for pregabalin.

Frequent harms for serotonin and norepinephrine reuptake inhibitors and anticonvulsants included dizziness, nausea, and somnolence, while studies of tricyclic antidepressants reported xerostomia, somnolence, and insomnia. For both opioids and atypical opioids, adverse effects were most frequently constipation, nausea, and somnolence. Dropout rates due to adverse effects varied widely from 2.5% up to 70% for oral agents and from 0% to 8.6% for nonoral agents.

“Our findings generally support the effectiveness of the 3 drugs approved by the Food and Drug Administration (FDA) for the treatment of pain in [diabetic peripheral neuropathy]: duloxetine, pregabalin, and tapentadol, although there was evidence of reporting bias for pregabalin,” the authors wrote. “The results also suggest that other, non-FDA approved agents may also be effective (oxcarbazepine, venlafaxine, TCAs, tramadol, and botulinum toxin). All these treatments also have substantial risks of adverse effects.”