Comparative efficacy and safety of gabapentin, pregabalin, oxcarbazepine, and duloxetine in diabetic peripheral neuropathy: A network meta-analysis

Perspect Clin Res. 2024 Oct-Dec;15(4):202-208. doi: 10.4103/picr.picr_218_23. Epub 2024 Jul 10.

Abstract

Purpose: To conduct a network meta-analysis comparing the safety and efficacy of gabapentin (GBP), pregabalin (PGB), oxcarbazepine (OXC), and duloxetine (DLX) in treating diabetic peripheral neuropathy (DPN).

Materials and methods: The study's eligibility criteria includee randomized controlled trials (RCTs) with a focus on DPN patients receiving GBP, PGB, DLX, or OXC versus placebo. Noncompliant trials with incomplete information and observational studies were excluded.

Results: Twelve (RCTs) of PGB, 2 of GBP, 3 of DLX, and 1 of OXC met the inclusion criteria. When drugs were compared for efficacy (direct comparison), GBP (Odd's ratio [OR] = 3.208, P < 0.001) was most effective followed by OXC (OR = 2.4, P = 0.0248), DLX (OR = 2.346, P < 0.001), and PGB (OR = 2.161, P < 0.001). When drugs were compared for withdrawal due to adverse drug reaction (ADR) (direct comparison), GBP (OR = 1.3818, P = 0.766) was safest followed by PGB (OR = 2.16, P < 0.001), DLX (OR = 2.469, P < 0.001), and OXC (OR = 4.4967, P = 0.001). Indirect comparison was done for efficacy, DLX was statistically significant than PGB and OXC (DLX vs. PGB, P = 0.03; DLX vs. OXC, P = 0.02). When indirect comparison was done for patient withdrawal due to ADR, OXC was worst (GBP vs. OXC, P = 0.0001; PGB vs. OXC, P = 0.007; DLX vs. OXC, P = 0.015). When drugs were compared for individual ADRs (direct comparison), dizziness was most commonly seen with OXC (OR = 9.6535, P = 1.8425), headache with OXC (OR = 3.8686, P = 0.006), somnolence with PGB (OR = 5.189, P < 0.001), and nausea with DLX (OR = 3.264, P < 0.001). GBP was most effective and safest drug followed by OXC > DLX > PGB for efficacy and PGB > DLX > OXC for safety.

Conclusion: In evaluating medications for DPN against placebo, GBP and OXC demonstrated the highest effectiveness while maintaining a favorable safety profile.

Keywords: Diabetic peripheral neuropathy; duloxetine; gabapentin; network meta-analysis; oxcarbazepine; pregabalin.