Efficacy and safety of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: A meta-analysis of randomized controlled trials.

Sodium glucose cotransporter-2 (SGLT2) is a sodium-dependent glucose transporter responsible for renal absorption of glucose. Dapagliflozin is an SGLT2 inhibitor used in patients with type 1 diabetes to promote urinary glucose excretion, but to date, randomized controlled trials (RCTs) to evaluate the effect of this drug in this disease have not been systematically evaluated. Therefore, the aim of the present study was to evaluate the efficacy and safety of dapagliflozin, as an adjuvant therapy to insulin, in the treatment of type 1 diabetes mellitus through a systematic review and meta-analysis. The Cochrane Library Database, Medline and Embase databases were used to search articles published between January 1st 2004 and February 5th 2020 with no language restrictions relating to RCTs. After extracting the data, the quality of the RCTs was evaluated and the data were statistically analyzed. A total of 4 RCTs with 1,691 participants were included. Dapagliflozin resulted in decreased glycosylated hemoglobin A1c (0.40-0.45%), body weight (2.52-3.85 kg), mean daily glucose (0.76-0.99 mmol/l) and mean amplitude of glucose excursion (0.54-1.07 mmol/l; all with P<0.00001) compared to placebo. Subgroup analysis by dose indicated no significant difference in all efficacy outcome indicators between dapagliflozin at 5 and at 10 mg (P>0.1). Compared with placebo, the use of dapagliflozin in patients with type 1 diabetes increased the risk of adverse events and serious adverse events (P<0.05), but did not increase the risks of infection, diabetic ketoacidosis (DKA) and discontinuation due to adverse events. Analysis by dose group suggested that no significant difference in all safety outcome indicators between dapagliflozin at 5 and at 10 mg (P>0.1). In conclusion, dapagliflozin had a significant effect on type 1 diabetes. However, the use of dapagliflozin significantly increased the incidence of adverse events and serious adverse events compared with placebo. Dapagliflozin-assisted short-term (24 weeks) insulin therapy for type 1 diabetes did not increase the risk of DKA but additional high-quality studies are required to determine its long-term efficacy and safety.