Sodium-Glucose Cotransporter 2 Inhibitors for Type 1 Diabetes Mellitus—Systematic Review and Meta-analysis

Abstract

Additional treatment for type 1 diabetes is an unmet need. We investigated the efficacy and safety of adding Sodium-glucose co-transporter 2 inhibitors (SGLT2is) to insulin in patients with type 1 diabetes mellitus by performing meta-analysis. Prospective randomized, placebo-controlled trials investigating insulin and SGLT2is in adults with type 1 diabetes were assessed. We searched electronic databases up to November 2017. Meta-analysis was performed by a random effects model. Two reviewers independently extracted information and evaluated study quality with the Cochrane risk-of-bias tool. Among about 1300 studies identified, 14 studies were investigated (N=4,591). Meta-analysis revealed that SGLT2i therapy significantly reduced HbA1c by 0.4% (95% confidence interval [CI]: 0.35, 0.46; P<0.001; I2=0%), fasting plasma glucose by 1.14 mmol/l (0.8,1.47), body weight by 2.68 kg (2.0, 3.36), and systolic blood pressure by 3.37 mmHg (1.46, 5.28). In addition, the total daily insulin dose decreased by 6.0 units (4.9, 7.1), bolus insulin decreased by 3.6 units/day (2.0, 5.3), and basal insulin decreased by 4.2 units/day (2.2, 6.3). There was no significant increase of hypoglycemia or severe hypoglycemia. However, SGLT2i therapy increased diabetic ketoacidosis [OR: 3.38 (1.74, 6.56)] and genital tract infection [OR: 3.44 (2.34, 5.07)]. In summary, SGLT2i therapy might be advantageous for type 1 diabetes. However, use of this combination should be considered carefully. Disclosure T. Yamada: None. J. Hosoe: None. N. Shojima: None. T. Yamauchi: Research Support; Self; Novo Nordisk Inc., Daiichi Sankyo Company, Limited, Sanofi, Takeda, Tanabe-Mitsubishi. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.