Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

Diabetes Obes Metab. 2017 Jan;19(1):142-147. doi: 10.1111/dom.12785. Epub 2016 Sep 29.

Abstract

Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose.

Keywords: SGLT2 inhibitor; insulin therapy; meta-analysis; type 2 diabetes.

Publication types

  • Meta-Analysis

MeSH terms

  • Benzhydryl Compounds / therapeutic use
  • Blood Glucose / metabolism
  • Body Weight
  • Canagliflozin / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Therapy, Combination
  • Glucosides / therapeutic use
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Reproductive Tract Infections / chemically induced
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Treatment Outcome
  • Urinary Tract Infections / chemically induced
  • Weight Loss

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • hemoglobin A1c protein, human
  • Canagliflozin
  • dapagliflozin
  • empagliflozin