Clinical adverse effects of sodium-glucose cotransporter 2 inhibitors: Protocol for a systematic review and meta-analysis.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral antidiabetic drugs, which mainly increase urinary glucose excretion through reducing renal glucose reabsorption. There is still a concern about the overall safety profile of SGLT2 inhibitors. In this systematic review and meta-analysis, we will assess the clinical adverse effects of SGLT2 inhibitors in type 2 diabetes mellitus.

Methods: This systemic review and meta-analysis described in this protocol will be conducted to follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We will search Medline, EMbase, the Cochrane library and the ClinicalTrials.gov Website from 1946 to June 2018. Studies will be screened by title, abstract, and full text independently in duplicate. Double-blinded, placebo-controlled, and randomized controlled trials reporting safety data of SGLT2 inhibitors will be eligible for inclusion. Outcomes will include adverse events (AEs) varying degrees and AEs occurring in ≥3% patients or AEs aroused concerns by the Food and Drug Administration (FDA). The assessment of risk bias and data synthesis will be performed using STATA software (version12, Statacorp, College Station, TX). Outcomes will be reported by risk ratios for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes and their 95% confidence intervals. Subgroup, sensitivity, regression analyses will be performed to evaluate intertrial heterogeneity and bias of the results. I statistic will be used to evaluate heterogeneity among studies.

Results: This systemic review and meta-analysis will evaluate AEs occurring in ≥3% patients or AEs aroused concerns by the FDA of SGLT2i as compared to placebo.

Conclusion: Our study will provide a comprehensive picture of AEs of SGLT2 inhibitors.