Efficacy and safety of duloxetine in painful diabetic peripheral neuropathy: a systematic review and meta-analysis of randomized controlled trials

Syst Rev. 2023 Mar 21;12(1):53. doi: 10.1186/s13643-023-02185-6.


Background: Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.

Methods: Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life.

Results: We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.

Conclusions: Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.

Systematic review registration: PROSPERO CRD42021225451.

Keywords: Duloxetine; Meta-analysis; Painful diabetic polyneuropathy; Systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Diabetes Mellitus*
  • Diabetic Neuropathies* / chemically induced
  • Diabetic Neuropathies* / drug therapy
  • Duloxetine Hydrochloride / therapeutic use
  • Humans
  • Pain / drug therapy
  • Quality of Life
  • Randomized Controlled Trials as Topic


  • Duloxetine Hydrochloride