Canagliflozin lowers HbA1c in children with T2D

Treatment with canagliflozin results in clinically meaningful reductions in glycated haemoglobin (HbA1c), when compared with placebo, in children and adolescents with type 2 diabetes (T2D), as shown by the results of a phase III study presented at EASD 2024.

In addition, canagliflozin is safe and well tolerated, with a safety profile similar to that seen in adults.

“Overall, the results of this study indicate that canagliflozin offers a new treatment option for children 10 years and older with T2D,” said lead study author Dr Saberi Rana Ali from Janssen Research & Development, LLC, a Johnson & Johnson Company, Raritan, New Jersey, US.

This randomized, double-blind, placebo-controlled phase III trial was conducted at 104 sites in 10 countries. Ali and her team enrolled children aged ≥10 to <18 years who had inadequate glycaemic control (HbA1c ≥6.5 percent to ≤11 percent) and were on diet and exercise alone or in combination with metformin monotherapy, insulin monotherapy, or metformin with or without insulin.

Eligible participants (mean age 14.3 years, 68.4 percent female, mean HbA1c 8.0 percent) were randomized to receive canagliflozin (n=84) or placebo (n=87) for 52 weeks, consisting of a 26-week core treatment period followed by 26 weeks of extended treatment.

At week 13, children treated with canagliflozin 100 mg with HbA1c ≥7 percent and eGFR ≥60 mL/min/1.73 m² were again randomized 1:1 to receive either canagliflozin 100 mg/placebo or canagliflozin 300 mg/placebo.

HbA1c reduction

The primary efficacy endpoint was the change in HbA1c at week 26 from baseline in the overall population and in the subset on background metformin with or without insulin, while the safety endpoints were safety and tolerability of canagliflozin.

Other key secondary endpoints included change from baseline in HbA1c at weeks 12 and 52 in all participants; change from baseline in fasting plasma glucose (FPG); proportion of participants with HbA1c <7.5 percent, <7 percent, and <6.5 percent at weeks 26 and 52; proportion of participants requiring rescue therapy; and time to rescue therapy.

Baseline characteristics did not significantly differ between the two treatment arms. At week 26, children on canagliflozin achieved a statistically significant decrease in HbA1c from baseline (least square mean difference, ‒0.76 percent, 95 percent confidence interval [CI], ‒1.25 to ‒0.27; p=0.002). [EASD 2024, abstract 50]

The reduction in HbA1c occurred as early as week 6 and persisted up to the end of trial. HbA1c trends were similar in the subset of patients on background metformin with or without insulin.

The canagliflozin arm also saw significant improvements in FPG at weeks 26 and 52. More patients on canagliflozin also achieved HbA1c <7 percent (54.9 percent vs 22.7 percent) and <6.5 percent (36.6 percent vs 12.0 percent) at week 52.

Patients who received rescue medications were fewer in the canagliflozin arm than the placebo arm (12 percent vs 46 percent), and those treated with canagliflozin had a longer time to rescue therapy. In addition, changes in Tanner stage characteristics were comparable between the two cohorts.

Safety profile

Sixty-five patients in each group (canagliflozin: 77.4 percent; placebo: 74.7 percent) reported treatment-emergent adverse events (TEAEs), while serious TEAEs occurred in eight (9.5 percent) and five (5.7 percent) children, respectively.

One patient in each group discontinued treatment due to AEs. None of the serious TEAEs or AEs leading to discontinuation were deemed associated with canagliflozin.

“Canagliflozin was found to be safe and effective and well tolerated in this population,” Ali said. “Safety profile was found to be similar to that seen in the adults.”