Prostaglandin E1 plus methylcobalamin combination therapy versus prostaglandin E1 monotherapy for patients with diabetic peripheral neuropathy A meta-analysis of randomized controlled trials

Background: Prostaglandin E1 (P) or methylcobalamin (M) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in many clinical trial reports. However, the combined effects of 2 drugs still remain dubious. Objective: The aim of this report was to evaluate the efficacy of M plus P (M+P) for the treatment of DPN compared with that of P monotherapy, in order to provide a reference resource for rational drug use. Methods: Randomized controlled trials (RCTs) of M+P for DPN published up to September 2017 were searched. Risk ratio (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I-2 test. Subgroup and sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects. Results: Sixteen RCTs with 1136 participants were included. Clinical efficacy of M+P combination therapy was significantly better than P monotherapy (fifteen trials; RR 1.25, 95% CI 1.18-1.32, P<.00001, I-2= 27%). Compared with P monotherapy, the pooled effects of M+P combination therapy on nerve conduction velocity were (MD 6.29, 95% CI 4.63-7.94, P<.00001, I-2= 90%) for median MNCV, (MD 5.68, 95% CI 3.53-7.83, P<.00001, I-2= 94%) for median SNCV, (MD 5.36, 95% CI 3.86-6.87, P<.00001, I-2= 92%) for peroneal MNCV, (MD 4.62, 95% CI 3.48-5.75, P<.00001, I-2= 86%) for peroneal SNCV. There were no serious adverse events associated with drug intervention. Conclusions: M+P combination therapy was superior to P monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients. Moreover, no serious adverse events occur in combination therapy.