AT THE ADA ANNUAL SCIENTIFIC SESSIONS
NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Compared with placebo, canagliflozin improved glycemic control and reduced glycemic variability over 18 weeks in adults with type 1 diabetes that had been inadequately controlled with insulin, according to results from a randomized trial.
“Patients with type 1 diabetes can experience acute and profound glucose fluctuations, which may be related to variability in insulin activity and changes in day-to-day activities,” Maria Alba, MD, said at the annual scientific sessions of the American Diabetes Association. “A major challenge in the treatment of type 1 diabetes is achieving patient-specific glycemic control while avoiding episodes of hyperglycemia and hypoglycemia.”
Canagliflozin is a sodium glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes; it lowers blood glucose through an insulin-dependent mechanism by lowering the renal threshold for glucose and increasing urinary glucose excretion. It is not approved for the treatment of type 1 diabetes. In a phase II study, canagliflozin improved glycemic control and provided reductions in body weight and insulin dose in patients with type 1 diabetes who were on background insulin over 18 weeks ( Diabetes Care 2015;39:2258-65 ).
The purpose of the current study was to assess the effects of canagliflozin on daily mean glucose, glycemic variability, and time spent in glycemic ranges (greater than 70-180 mg/dL) in adults with type 1 diabetes inadequately controlled with insulin therapy, said Dr. Alba of Janssen Research & Development, Raritan, N.J. In all, 351 patients were randomized to placebo or 100 mg or 300 mg of canagliflozin. All had had the disease for at least 1 year, had a baseline hemoglobin A1c level between 7% and 9%, and had to be on a stable insulin regimen for at least 8 weeks. “On the day before randomization, patients were advised to reduce their basal insulin by 10% or 20%, depending on their baseline A1c,” she said. “Once randomized, they were instructed to titrate their insulin to reach specific glycemic goals.”
All patients were to record 9-point self-monitoring blood glucose (SMBG) measurements throughout the study. Continuous glucose monitoring (CGM) assessments were performed at selected study centers in a substudy of 89 patients. Efficacy endpoints assessed by 9-point SMBG at week 18 were change from baseline in mean daily glucose and daily glucose standard deviation. Efficacy endpoints in the CGM substudy at week 18 were change from baseline in mean glucose, patterns of glucose variability, and time spent within target glucose (greater than 70-180 mg/dL), above target (greater than 180 mg/dL), or below target (70 mg/dL or less). The mean age of study participants was 43 years, 55% were male, and their mean baseline A1c was 7.9%.
At 18 weeks, reductions in daily mean glucose were observed in the canagliflozin 100-mg and 300-mg groups, compared with placebo (–22.4 and –19.4 mg/dL, respectively, vs. a rise of 3 mg/dL in the placebo group), as well as reductions in daily glucose standard deviation (–16.4 and –18.1 mg/dL, vs. –1.9 mg/dL), Dr. Alba reported.
The researchers also found that the percentage of time spent within the glycemic target range was greater in the canagliflozin 100- and 300-mg groups, compared with placebo (a change from baseline of 11.6% and 10.1%, respectively, compared with a decrease of 3.5%), while the percentage of time spent above target was lower in both canagliflozin doses, compared with placebo. Canagliflozin was generally well tolerated, with a dose-dependent increase in ketone-related adverse events (5.1% in the 100-mg group and 9.4% in the 300-mg group).
Janssen Research & Development supported the study.