To evaluate the efficacy of pharmacological interventions in managing pain in diabetic peripheral neuropathy (DPN) through a network meta-analysis (NMA) and systematic review.

Over 50% of patients with diabetes eventually develop peripheral neuropathy, which can be painful and disabling. The optimal choice of pharmacotherapy for achieving pain relief remains unclear, and a comprehensive review of evidence incorporating recent data is warranted to establish effective pain management strategies and compare their efficacies.

A thorough systematic search was conducted in the databases: PubMed/MEDLINE, Cochrane, EMBASE, and ClinicalTrials.gov databases to identify RCTs that focused on interventions for DPN. The search included trials from the earliest available date up to September 2023. The primary outcome considered was a 50% reduction in pain. Pairwise meta-analysis and network meta-analysis were performed using the frequentist approach to obtain direct and indirect comparisons of each measure in terms of risk ratios.

A total of 57 RCTs with 13,132 patients and 43 different pharmacological interventions provided data on pain reduction of 50% or more (the largest analysis to date). Compared to placebo, more than 50% decrease in pain intensity was only seen with Pregabalin [RR 1.35; 1.05-1.73],Duloxetine [RR 1.51;1.10-2.05], Gabapentin [RR 1.99;1.07-3.68], and Oxcarbazepine [RR 2.55;95% CI: 1.15-5.65] in this order of increasing efficacy. However, no significant difference in efficacy between the four drugs was observed.

This preliminary analysis confirms that Pregabalin, Duloxetine, Gabapentin, and Oxcarbazepine have substantial pain relief in diabetic peripheral neuropathy compared to placebo. Further comprehensive and in-depth analysis is currently underway.