Sodium–glucose cotransporter inhibitors as add-on therapy in addition to insulin for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials

Abstract

Aims/Introduction: Several clinical trials reported the effects of sodium–glucose cotransporter (SGLT) inhibitors in type 1 diabetes patients. This meta-analysis aimed to assess the efficacy and safety of SGLT inhibitors in type 1 diabetes patients. Materials and Methods: Relevant studies were identified in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases through 1 April 2020. Differences were expressed as the 95% confidence interval (CI) or weighted mean difference (WMD) for continuous outcomes, and risk ratio (RR) for discontinuous outcomes. Results: A total of 13 RCTs with 7,962 cases were included. SGLT inhibitors reduced the fasting plasma glucose level (WMD −1.320 mmol/L, 95% CI −1.609 to −1.031, P < 0.001), glycated hemoglobin level (WMD −0.386%, 95% CI −0.431 to −0.342, P < 0.001) and daily total insulin dose (WMD −5.403, 95% CI −7.218 to −3.859, P < 0.001). However, higher risks of diabetic ketoacidosis (RR 5.042, 95% CI 3.160–8.046, P < 0.001), urinary tract infections (RR 1.259, 95% CI 1.034–1.533,P = 0.022) and genital infections (RR 2.995, 95% CI 1.953–4.594, P < 0.001) were associated with SGLT inhibitors, but SGLT inhibitors did not increase the hypoglycemia risk (RR 0.980, 95% CI 0.840–1.144,P = 0.799). In subgroup analysis, with a significant reduction of fasting plasma glucose, glycated hemoglobin and daily insulin doses, SGLT1/2 inhibitor did not increase genitourinary tract infections compared with a placebo. Conclusions: SGLT2 and SGLT1/2 inhibitors can improve glycemic control in patients with type 1 diabetes.