Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison

Abstract

Objective: To determine whether duloxetine is noninferior to (as good as) pregabalin in the treatment of pain associated with diabetic peripheral neuropathy.

Patients and methods: We performed a 12-week, open-label study of patients with diabetic peripheral neuropathic pain who had been treated with gabapentin (≥ 900 mg/d) and had an inadequate response (defined as a daily pain score of ≥ 4 on a numerical rating scale [0-10 points]). The first patient was enrolled on September 28, 2006, and the last patient visit occurred on August 26, 2009. Patients were randomized to duloxetine monotherapy (n=138), pregabalin monotherapy (n=134), or a combination of duloxetine and gabapentin (n=135). The primary objective was a noninferiority comparison between duloxetine and pregabalin on improvement in the weekly mean of the diary-based daily pain score (0- to 10-point scale) at end point. Noninferiority would be declared if the mean improvement for duloxetine was no worse than the mean improvement for pregabalin, within statistical variability, by a margin of -0.8 unit.

Results: The mean change in the pain rating at end point was -2.6 for duloxetine and -2.1 for pregabalin. The 97.5% lower confidence limit was a -0.05 difference in means, establishing noninferiority. As to adverse effects, nausea, insomnia, hyperhidrosis, and decreased appetite were more frequent with duloxetine than pregabalin; insomnia, more frequent with duloxetine than duloxetine plus gabapentin; peripheral edema, more frequent with pregabalin than with duloxetine; and nausea, hyperhidrosis, decreased appetite, and vomiting, more frequent with duloxetine plus gabapentin than with pregabalin.

Conclusion: Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin.

Trial registration: clinicaltrials.gov Identifier: NCT00385671.

FIGURE 1.

Patient disposition diagram showing the flow of patients through each stage of the trial from screening through completion.

FIGURE 2.

Results of the noninferiority test for duloxetine vs pregabalin. Changes from baseline to week 12 in the weekly mean of the daily pain severity for duloxetine- and pregabalin-treated patients were –2.6 and –2.1, respectively (treatment difference, 0.49; 95% confidence interval [CI], –0.05 to 1.04; P=.08).

FIGURE 3.

Changes in weekly means of the daily pain severity ratings from patient diaries. Significant superiority vs pregabalin was seen in some weeks before week 12 for duloxetine monotherapy and for duloxetine + gabapentin combination therapy.