A Phase III, international, randomized clinical trial assessed the safety and efficacy of canagliflozin for the treatment of type 2 diabetes mellitus (T2DM) in children and adolescents.

The study found canagliflozin provided significantly greater and clinically meaningful reductions in HbA1c compared with placebo, and the safety profile was like that seen in adults. The results support the use of canagliflozin for T2DM in children and adults, a population where treatment options are very limited.

The findings are published in Annals of Internal Medicine.

Researchers from Johnson & Johnson studied data from 171 children aged 10 to 18 years with T2DM and inadequate glycemic control between 28 July 2017 and 20 September 2023 at 104 sites across 10 countries.

Participants were randomly assigned 1:1 to receive either oral canagliflozin (100 mg) or matching placebo once daily. Their HbA1c and estimated glomerular filtration rate (eGFR) were assessed at week 12.

At the week 13 visit, participants with week 12 readings of 7% or higher for HbA1c and at least 60 mL/min/1.73 m² for eGFR were randomly assigned again to either continue receiving their original treatment assignment or have their dose uptitrated from 100 mg/d to 300 mg/d or matching placebo.

Treatment continued for a total of 52 weeks. The primary efficacy endpoint was change in HbA1c at week 26. Key secondary endpoints included change in HBA1c at week 52, change in fasting plasma glucose, and change in body weight at weeks 26 and 52. Safety assessments included monitoring for adverse events (AEs) and adverse events of special interest, including hypoglycemic events.

The researchers found that at week 26, participants receiving canagliflozin had significantly greater HbA1c improvement compared to those who received placebo. A sensitivity analysis showed improvement in HbA1c as early as week six that was maintained through the end of study treatment.

At week 52, a greater proportion of participants receiving canagliflozin had an HBA1c less than 6.5% (MP, 30.9% vs. 15.6%; difference in MP, 15.2 percentage points [CI, 3.4 to 27.1 percentage points]) or less than 7.0% (MP, 47.2% vs. 28.9%; difference in MP, 18.3 percentage points [CI, 6.6 to 30.0 percentage points]).

Fasting plasma glucose levels significantly improved at week 26 in participants receiving canagliflozin compared to placebo.

The most common treatment-emergent AEs among participants taking canagliflozin were headaches, nasopharyngitis, urinary tract infection, and vomiting. The risk of hypoglycemic events was low, with no severe hypoglycemic events occurring with canagliflozin treatment. The results show that canagliflozin is safe, effective, and well-tolerated among children and adolescents aged 10 to 18 years with T2DM.