The comparison of efficacy and safety between different doses of empagliflozin in insulin-treated type 1 diabetes mellitus patients: a systematic review and meta-analysis protocol.

OBJECTIVES: The proposed review aims to compare the efficacy and safety profile of empagliflozin 25 mg with its lower dosages and placebo, respectively, in insulin-treated type 1 diabetes mellitus (T1DM) patients.
METHODS: Double-blinded randomized controlled trials comparing the above outcomes will be searched primarily in three electronic databases (PubMed, Embase, and Scopus) and eligible trials will be included in the proposed review. Then, from the trials recruited in the review, data of the study design, participants, interventions compared, and outcomes of interest will be extracted. Subsequently, the trials' risk of bias will be assessed using the Cochrane Collaboration's tool. The meta-analysis will be conducted with a fixed-effect or a random-effect model to estimate the mean differences (weighted or standardized) and risk ratios for the efficacy and safety-related comparable outcome data, respectively. Statistical heterogeneity will be assessed by the p-value of chi-squared statistics and I2 statistics and explained by subgroup analysis and meta-regression. Publication bias will be assessed by funnel plots and Egger's test. The sensitivity analysis will repeat the meta-analysis for respective outcomes using assumptions alternative to that used in the preliminary meta-analysis and by dropping each study at a time.
RESULTS: A narrative reporting will ensue if a meta-analytic comparison is not possible.
CONCLUSIONS: Based on the contemporary literature, the proposed review will synthesize the evidence on how the efficacy and safety profile of high dose empagliflozin varies with its lower doses and placebo, respectively, in insulin-treated T1DM patients. © Springer Nature Switzerland AG 2020.