Combination Therapy in Painful Diabetic Neuropathy: A Scoping Review

Diabetic neuropathy is the most common microvascular complication of Diabetes Mellitus. Approximately one-third of patients with Diabetic Neuropathy experience clinical features that fit the Painful Diabetic Neuropathy spectrum. Many studies have discussed the effectiveness of monotherapy in PDN. Recommendations indicate that if pain is not resolved with monotherapy then drug combination therapy can be considered. This scoping review follows the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement guideline and the PCC (Population-Concept-Context) framework. We conducted a structured literature search in PubMed, ScienceDirect, EBSCOhost, and ProQuest from the beginning until August 2023 to identify all published articles on the efficacy and safety of combination therapy. The Mixed Methods Appraisal Tool (MMAT) was used to evaluate the quality of evidence in each included article. We gathered 15 relevant publications including 20 studies in the present scoping review. Three outcomes were evaluated, clinical effectiveness, clinical safety, and cost-effectiveness. Common clinical effectiveness outcomes observed included significant pain relief, nerve function improvement, and sleep improvement in combination therapy over monotherapy. Pain improvement in combination was mostly observed by using Pregabalin. Nerve function improvement was mostly observed using Methylcobalamin. More studies showed no difference in clinical safety between combination and monotherapy. The overall cost of monotherapy and combination therapy also did not differ significantly. In conclusion, combination therapy potentially showed better results in terms of clinical outcomes and safety profile but not in cost-effectiveness compared to monotherapy in the management of PDN.