The Effect of Canagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, on Glycemic End Points Assessed by Continuous Glucose Monitoring and Patient-Reported Outcomes Among People With Type 1 Diabetes

Diabetes Care. 2017 Feb;40(2):171-180. doi: 10.2337/dc16-1353. Epub 2016 Nov 29.

Abstract

Objective: To assess the effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic parameters and measures of glucose variability assessed by a 9-point self-monitoring blood glucose (SMBG) and continuous glucose monitoring (CGM) profiles, and patient-reported outcomes as an add-on to insulin among participants with type 1 diabetes.

Research design and methods: In this randomized, double-blind study, 351 participants received canagliflozin 100 or 300 mg or placebo for 18 weeks. Change from baseline in daily mean glucose and SD was measured using a 9-point SMBG profile. In a subset of 89 participants who underwent CGM, the change from baseline in mean glucose, measures of glycemic variability (SD, coefficient of variation, and mean amplitude of glycemic excursions), and time spent in glycemic ranges were assessed. Change in treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire (n = 328).

Results: At week 18, reductions in daily mean glucose and SD measured using the 9-point SMBG profile were seen with canagliflozin 100 and 300 mg versus placebo. Reductions in mean glucose (-1.2, -0.7, and 0.6 mmol/L) and measures of glycemic variability assessed by CGM, such as changes in glucose SD (-0.3, -0.7, and 0.1 mmol/L), were also seen with canagliflozin 100 and 300 mg versus placebo, respectively. Canagliflozin 100 and 300 mg were associated with increases in time spent within target (glucose >3.9 to ≤10.0 mmol/L) compared with placebo (11.6%, 10.1%, and -3.5%, respectively) and commensurate reductions in time spent above the target level (glucose >10.0 mmol/L; -12.7%,-7.6%, and 5.7%, respectively). Participants showed greater improvement in treatment satisfaction with canagliflozin versus placebo; reductions in insulin dose, SD of glucose, and body weight contributed to the relationship between canagliflozin and satisfaction change.

Conclusions: Canagliflozin improved indices of glycemic variability and was associated with improvement in treatment satisfaction versus placebo over 18 weeks among participants with type 1 diabetes. Although these data from this study demonstrate the potential benefits of canagliflozin in people with type 1 diabetes, canagliflozin is not approved for the treatment of type 1 diabetes and should not currently be used in people with type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT02139943.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose Self-Monitoring
  • Canagliflozin / therapeutic use*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / pharmacology
  • Logistic Models
  • Male
  • Middle Aged
  • Patient Reported Outcome Measures*
  • Sodium-Glucose Transporter 2 / metabolism*
  • Sodium-Glucose Transporter 2 Inhibitors

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin

Associated data

  • ClinicalTrials.gov/NCT02139943