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

J Diabetes Investig. 2021 Apr;12(4):546-556. doi: 10.1111/jdi.13387. Epub 2020 Sep 19.

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.

Keywords: Diabetes mellitus type 1; Effects; Sodium-glucose cotransporter inhibitors.

Publication types

  • Meta-Analysis

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Genital Diseases / chemically induced
  • Glycemic Control
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Urinary Tract Infections / chemically induced

Substances

  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors