Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes

Diabetes Care. 2015 Mar;38(3):403-11. doi: 10.2337/dc14-1237. Epub 2014 Dec 2.

Abstract

Objective: There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin.

Research design and methods: The CANagliflozin CardioVascular Assessment Study is a double-blind, placebo-controlled study that randomized participants to placebo, canagliflozin 100 mg, or canagliflozin 300 mg once daily, added to a range of therapies. The primary end point of this substudy was the change in HbA1c from baseline at 18 weeks among patients using insulin; 52-week effects were also examined.

Results: Individuals receiving insulin at baseline were randomized to receive placebo (n = 690), canagliflozin 100 mg (n = 692), or canagliflozin 300 mg (n = 690). These individuals were 66% male and had a median age of 63 years, mean HbA1c of 8.3% (67 mmol/mol), BMI of 33.1 kg/m(2), estimated glomerular filtration rate of 75 mL/min/1.73 m(2), fasting plasma glucose of 9.2 mmol/L, and a median daily insulin dose of 60 IU. Most individuals were using basal/bolus insulin. Reductions in HbA1c with canagliflozin 100 and 300 mg versus placebo were -0.62% (95% CI -0.69, -0.54; -6.8 mmol/mol [95% CI -7.5, -5.9]; P < 0.001) and -0.73% (95% CI -0.81, -0.65; -8.0 mmol/mol [95% CI -8.9, -7.1]; P < 0.001) at 18 weeks and -0.58% (95% CI -0.68, -0.48; -6.3 mmol/mol [95% CI -7.4, -5.2]) and -0.73% (95% CI -0.83, -0.63; -8.0 mmol/mol [95% CI -9.1, -6.9]) at 52 weeks. There were significant falls in fasting plasma glucose, body weight, and blood pressure at both time points and there was a greater incidence of hypoglycemia, genital mycotic infections, and hypovolemia with both canagliflozin doses.

Conclusions: Canagliflozin added to insulin therapy improved glycemic control and decreased body weight. There was a greater frequency of several anticipated side effects, although few led to discontinuation of treatment.

Trial registration: ClinicalTrials.gov NCT01032629.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Canagliflozin
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glucosides / administration & dosage*
  • Glucosides / adverse effects
  • Glycated Hemoglobin A / drug effects
  • Glycosuria / chemically induced
  • Humans
  • Hypoglycemia / drug therapy
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypovolemia / chemically induced
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Male
  • Middle Aged
  • Mycoses / chemically induced
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects
  • Treatment Outcome
  • Urinary Tract Infections / chemically induced
  • Weight Loss / drug effects

Substances

  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • Canagliflozin

Associated data

  • ClinicalTrials.gov/NCT01032629