Evaluation of the safety of sodium-glucose co-transporter-2 inhibitors for treating patients with type 1 diabetes

Aim To conduct an overall safety assessment of sodium-glucose co-transporter-2 (SGLT-2) inhibitors used for the treatment of patients with type 1 diabetes (T1D), including ketoacidosis, genital infection, volume depletion, liver and kidney injury events, cardiovascular events, diarrhea and severe hypoglycaemia. Materials and Methods We searched three databases (Pubmed, Embase and the Cochrane Library) for randomized controlled trials that treated T1D by using SGLT-2 inhibitors from 2000 to 5 March 2020. Results Of the 1653 articles identified that fit our search criteria, 22 studies included qualitative-based results, eight of which were randomized clinical trials that included quantitative-based results. Compared with the control group, the SGLT-2 inhibitors treatment group was found to have had an increased incidence of ketoacidosis (P< .00001, OR 4.34, 95% CI [2.37, 7.96], I-2= 18%), events leading to discontinuation (P< .0001, OR 1.76, 95% CI [1.34, 2.31], I-2= 0%), genital infection (P< .00001, OR 3.64, 95% CI [2.82, 4.70], I-2= 0%), volume depletion (P= .006, OR 2.10, 95% CI [1.23, 3.59], I-2= 4%) and diarrhoea (P= .008, OR 1.64, 95% CI [1.14, 2.36], I-2= 0%). However, according to subgroup analysis, the risk of diarrhoea was dose-related. The incidence of urinary tract infection, cardiovascular events, renal events, liver injury and fracture was not significantly different for the treatment group compared with the control group. Conclusions Despite showing some promise as a treatment approach, the application of SGLT-2 inhibitors for patients with T1D should be considered with caution.