Comparative Efficacy of Gabapentin and Duloxetine for Painful Diabetic Peripheral Neuropathy

diabetic neuropathy
This systematic review and meta-analysis of randomized controlled trials assessed the efficacy and safety of gabapentin and duloxetine for treating patients with painful diabetic peripheral neuropathy.

According to a recent study published in The International Journal of Clinical Practice, there is no significant difference between the use of gabapentin or duloxetine for the treatment of painful diabetic peripheral neuropathy (PDPN).

Gabapentin is an anticonvulsant that has demonstrated efficacy in PDPN treatment, and duloxetine is a norepinephrine-serotonin reuptake inhibitor also recommended for PDPN and commonly used for major depressive disorder. Only a few meta-analyses compare the 2 drug treatments for PDPN in randomized controlled trials (RCTs). This study comprises a systematic review and meta-analysis of RCTs that assess the efficacy and safety of these 2 drugs in patients with PDPN.

The literature search included articles from 2000 to 2021 using PubMed, Embase, and the Cochrane Library. Eligible studies were RCTs comparing duloxetine and gabapentin for PDPN and had outcomes that included pain intensity, clinical conditions, and adverse effects.

The researchers retrieved 776 articles; 492 of them were eligible for this study, and 3 RCTs met the inclusion criteria for the meta-analysis. The RCTs, which were conducted in India and Iran, were published in 2012, 2019, and 2020. The 3 studies included 290 patients with PDPN who received duloxetine or gabapentin. Patients in the duloxetine group received doses of 20 mg to 80 mg/day, whereas those in the gabapentin group received doses of 300 mg to 1200 mg/day.

The Visual Analogue Scale (VAS) score was used to assess for pain intensity of patients using duloxetine and gabapentin as reported in the 3 studies. VAS scores were obtained at baseline and weeks 4, 8, and 12. The mean change difference was 2.40 (95% CI, -5.57 to 10.37). All in all, no statistically significant difference was shown between the effect of duloxetine and gabapentin for PDPN (mean change difference, -1.23, 95% CI, -6.09 to 3.62; P =.62; heterogeneity, I2 =16%).

No statistically significant difference was observed between the effects of duloxetine and gabapentin for pain-related sleep interference, the Clinical or Patient Global Impression of Change, the patients’ Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathic Examination (DNE) score, and Neuropathic Disability Score (NDS).

In the study, 70 of 290 patients in the study experienced side effects. Those most commonly reported in the duloxetine group were nausea and vomiting (13.1%), somnolence (3.4%), and sleeplessness and dizziness (2.6%). Among patients who were treated with gabapentin, the most common side effects were nausea and vomiting (9.7%), sleeplessness (4.1%), and imbalance (2.1%).

The limitations of this study included a relatively insufficient sample size. Potential bias may have arisen from the protocols of the 3 studies not being standardized. Patients were followed for only 12 weeks at most so long-term differences in safety and efficacy between the 2 drug treatments were not studied.

This study concluded that there is no significant difference between duloxetine and gabapentin for treating PDPN and that the efficacies of the 2 drugs are equal. The study researchers recommended that clinicians organize management of patients with diabetes mellitus based on drug prices and the fewest side effects. Research is needed to determine the long-term effects of duloxetine and gabapentin for the treatment of PDPN.


Ko YC, Lee CH, Wu CS, Huang YJ. Comparison of efficacy and safety of gabapentin and duloxetine in painful diabetic peripheral neuropathy: a systematic review and meta-analysis of randomised controlled trials. Int J Clin Pract. Published online June 25, 2021. doi:10.1111/ijcp.14576