title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00385671.
authors: Division of Endocrinology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors: Robert J
authors: RJ
authors: Tanenberg
authors: Gordon A
authors: GA
authors: Irving
authors: Richard C
authors: RC
authors: Risser
authors: Jonna
authors: J
authors: Ahl
authors: Michael J
authors: MJ
authors: Robinson
authors: Vladimir
authors: V
authors: Skljarevski
authors: Sandra K
authors: SK
authors: Malcolm
mesh_terms: D000368:Aged; D000588:Amines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D000069583:Pregabalin; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D013876:Thiophenes; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000068736:Duloxetine Hydrochloride