OBJECTIVE:To evaluate the efficacy of α-lipoic acid (ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy (DPN).DATA SOURCES:The electronic databases of PubMed,Medline,Embase,the Cochrane Library,the Chinese National Knowledge Infrastructure,the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions.The search was conducted from the inception of each database to 7 October 2016.The key terms were (diabetic peripheral neuropathy or diabetic neuropathy or DPN) AND (α-lipoic acid or lipoic acid or thioctic acid) AND epalrestat.DATA SELECTION:All of the eligible studies met the following inclusion criteria:(1) Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.(2) The minimum duration of treatment was 2 weeks.(3) The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.(4) Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities.Studies in which the control group used epalrestat or ALA combined with other drugs were excluded.Statistical analyses were performed using STATA software for meta-analysis.OUTCOME MEASURES:The primary outcomes were the therapeutic efficacy,median motor nerve conduction velocity (MNCV),median sensory nerve conduction velocity (SNCV),peroneal MNCV and peroneal SNCV.RESULTS:Twenty studies with 1894 DPN patients were included,including 864 patients in the ALA plus epalrestat group,473 in the ALA group and 557 in the epalrestat group.The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies (RR =1.29,95％ CI:1.21-1.38;RR =1.43,95％ CI:1.34-1.54,respectively).ALA plus epalrestat combination therapy also significantly improved median MNCV (WMD =5.41,95％ CI:2.07-8.75),median SNCV (WMD =5.87,95％ CI:1.52-10.22),peroneal MNCV (WMD =5.59,95％ CI:2.70-8.47) and peroneal SNCV (WMD =4.57,95％ CI:2.46-6.68).CONCLUSION:ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.