Monotherapy Versus Combination Therapy in the Treatment of Painful Diabetic Neuropathy: A Systematic Review and Meta-analysis

Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy. PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95