A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing the Safety of Dapagliflozin in Type 1 Diabetes Patients

Background and Purpose: The dapagliflozin’s safety profile in insulin-treated adult type-1 diabetes mellites (T1DM) patients remains poorly explored. Therefore, this systematic review and meta-analysis compared the risk of all-cause side effects, study discontinuation of participants due to side effects, urinary tract infection (UTI), diabetic ketoacidosis, and hypoglycemia between dapagliflozin 10 mg and dapagliflozin 5 mg, dapagliflozin 10 mg and placebo, and dapagliflozin 5 mg and placebo. Materials and Methods: Parallel-arm randomized controlled trials juxtaposing the above outcomes between the afore-mentioned interventions were eligible for inclusion in this study and were searched in PubMed, Embase, and Scopus. Utilizing the Cochrane tool, the risk of bias was assessed in the recruited trials. Finally, by random-effect meta-analysis, each outcome was compared among the above interventions, and the risk ratio was estimated. Results: Four trials of varying length (1-52 weeks) sourcing data from almost 1760 participants from about 32 nations were reviewed. Overall, the trials had a low or unclear risk of bias, and only one was at a high risk of bias.  Compared to the placebo, the risk of side effects was higher in those treated with dapagliflozin 5 mg (RR=1.10; 95% CI=1.02-1.18; p=0.014; I2=0%). UTI risk was less with the 10mg dapagliflozin than its lower dose (RR=0.50; 95% CI=0.32-0.79; p-value=0.003; I2=0%). All the remaining comparisons were statistically not significantly different between the juxtaposed intervention pairs. Conclusion: In contrast to placebo, dapagliflozin 5mg increased the risk of overall adversities in insulin-treated type-1 diabetes, and dapagliflozin 10 mg had a reduced risk of UTI than its 5mg preparation.