Sodium-glucose cotransporter 2 inhibitors for diabetic neuropathy: a protocol for a systematic review and meta-analysis.

Abstract

Diabetic neuropathy is one of the most common and disabling complications of diabetes mellitus. Current management strategies are largely limited to glycaemic control and symptomatic relief, and few therapies have demonstrated definitive disease-modifying effects. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown multiple metabolic and vascular benefits. However, the efficacy and safety of SGLT2 inhibitors as adjunctive therapy for diabetic neuropathy have not yet been systematically evaluated. This protocol aims to describe the methodology for a systematic review and meta-analysis that will comprehensively assess the therapeutic value of SGLT2 inhibitors in diabetic neuropathy. A systematic search will be conducted in PubMed, Embase, Cochrane Library and Web of Science, as well as in clinical trial registries including the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov, from database inception to 31 May 2026. Eligible studies will include randomised controlled trials evaluating SGLT2 inhibitors in combination with conventional therapy in patients with diabetic neuropathy. Two reviewers will independently perform study selection, data extraction and methodological quality assessment. Extracted data will include study characteristics, participant demographics, intervention details, outcome measures and adverse events. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool. Quantitative synthesis will be conducted using meta-analytic methods, with the choice of statistical model determined by the degree of heterogeneity, as assessed by Cochran's Q test and the I² statistic. Where appropriate, meta-regression, subgroup analyses, sensitivity analyses and trial sequential analysis will be performed. Publication bias will be assessed using funnel plots and Egger's regression test, and the certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Ethical approval is not required because this study will involve only the analysis of published data. The findings will be disseminated through publication in a peer-reviewed journal. CRD420261389933.