OBJECTIVE: To compare the efficacy and tolerability of duloxetine (DLX) with pregabalin (PGB) and gabapentin (GBP) for the treatment of diabetic peripheral neuropathic pain (DPNP). METHODS: We searched PubMed, Ovid, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB and GBP in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24hPS) for all three drugs, and response rate (>50% pain reduction) and Patient's Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria were: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Pooled fixed- and random-effects analyses were conducted on endpoints reported in at least two studies of each drug. Each drug was compared with placebo. DLX was compared indirectly with PGB and GBP by meta-regression. RESULTS: Three studies of DLX, 6 of PGB and 2 of GBP were eligible. Between-study heterogeneity was insignificant. In random-effects and fixed-effects analyses, all drugs were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24hPS, but significant differences in PGI-I/C, favouring PGB, and dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences. CONCLUSIONS: From the few studies available for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.