Jiang De-Qi, Xu Lan-Cheng, Jiang Li-Lin, Li Ming-Xing, Wang Yong
College of Biology and Pharmacy, Yulin Normal University Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou Department of Pharmacy, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Medicine (Baltimore). 2018 Jul;97(27):e11390. doi: 10.1097/MD.0000000000011390.
Fasudil (F) plus methylcobalamin (M) or lipoic acid (L) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in numerous studies. However, the effect of the combined use still remains dubious.
The aim of this report was to evaluate the efficacy of F plus M or L (F + M or F + L) for the treatment of DPN compared with that of M or L monotherapy, respectively, in order to provide the basis and reference for clinical rational drug use.
Randomized controlled trials (RCTs) of F for DPN published up to September 2017 were searched. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (NCVs) (MNCVs), median sensory NCV (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects.
Thirteen RCTs with 1148 participants were included. Clinical efficacy of F + M combination therapy was significantly better than M monotherapy (8 trials; RR 1.26, 95% CI 1.17-1.35, P < .00001, I = 0%), the efficacy of F + L combination therapy was also obviously better than L monotherapy (4 trials; RR 1.27, 95% CI 1.16-1.39, P < .00001, I = 0%). Compared with monotherapy, the pooled effects of combination therapy on NCV were (MD 6.69, 95% CI 4.74-8.64, P < .00001, I = 92%) for median MNCV, (MD 6.71, 95% CI 1.77-11.65, P = .008, I = 99%) for median SNCV, (MD 4.18, 95% CI 2.37-5.99, P < .00001, I = 94%) for peroneal MNCV, (MD 5.89, 95% CI 3.57-8.20, P < .00001, I = 95%) for peroneal SNCV. Furthermore, there were no serious adverse events associated with drug intervention.
Combination therapy with F plus M or L was superior to M or L monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients, respectively. Moreover, no serious adverse events occur in combination therapy.
在众多研究中,已提出法舒地尔(F)联合甲钴胺(M)或硫辛酸(L)治疗作为糖尿病周围神经病变(DPN)的一种治疗方法。然而,联合使用的效果仍存在疑问。
本报告旨在评估F联合M或L(F+M或F+L)治疗DPN的疗效,并分别与M或L单药治疗进行比较,以便为临床合理用药提供依据和参考。
检索截至2017年9月发表的关于F治疗DPN的随机对照试验(RCT)。计算相对危险度(RR)、平均差(MD)和95%置信区间(CI),并采用I²检验评估异质性。还进行了敏感性分析。测量的结局如下:临床疗效、正中运动神经传导速度(NCV)(MNCV)、正中感觉NCV(SNCV)、腓总神经MNCV、腓总神经SNCV和不良反应。
纳入13项RCT,共1148名参与者。F+M联合治疗的临床疗效显著优于M单药治疗(8项试验;RR 1.26,95%CI 1.17-1.35,P<0.00001,I²=0%),F+L联合治疗的疗效也明显优于L单药治疗(4项试验;RR 1.27,95%CI 1.16-1.39,P<0.00001,I²=0%)。与单药治疗相比,联合治疗对NCV的合并效应为:正中MNCV(MD 6.69,95%CI 4.74-8.64,P<0.00001,I²=92%),正中SNCV(MD 6.71,95%CI 1.77-11.65,P=0.008,I²=99%),腓总神经MNCV(MD 4.18,95%CI 2.37-5.99,P<0.00001,I²=94%),腓总神经SNCV(MD 5.89,95%CI 3.57-8.20,P<0.00001,I²=95%)。此外,未发现与药物干预相关的严重不良事件。
F联合M或L的联合治疗分别在改善DPN患者的神经病变症状和NCV方面优于M或L单药治疗。此外,联合治疗未发生严重不良事件。