Article Impact Level: HIGH Data Quality: STRONG Summary of Annals of Internal Medicine, ANNALS-24-04017. https://doi.org/10.7326/ANNALS-24-04017 Dr. Ulhas Nadgir et al.
Points
- Canagliflozin significantly reduced HbA1c levels from baseline to week 26 compared to placebo, showing a mean difference of −0.76% in this pediatric and adolescent population with type 2 diabetes mellitus (T2DM).
- A greater proportion of participants receiving canagliflozin achieved an HbA1c level below 6.5% at week 26, demonstrating superior glycemic control over the placebo group.
- Significant improvements in glycemic control, including lower HbA1c and fasting plasma glucose levels, were observed as early as week six and were maintained throughout the 52-week study period.
- The overall safety profile was comparable to that seen in adults, with common adverse events including headache, nasopharyngitis, urinary tract infection, and vomiting.
- The risk of hypoglycemia was low and similar between the canagliflozin and placebo groups, and no severe hypoglycemic events were reported with canagliflozin treatment.
Summary
A phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of canagliflozin in 171 children and adolescents aged 10 years or older with type 2 diabetes mellitus (T2DM) and a baseline hemoglobin A1c (HbA1c) between 6.5% and 11%. Participants were randomly assigned 1:1 to receive oral canagliflozin 100 mg or placebo once daily. At week 13, participants with an HbA1c of 7% or higher and an eGFR of at least 60 mL/min/1.73 m2 were re-randomized to either continue their assigned dose or uptitrate to 300 mg (or matching placebo) for a total treatment period of 52 weeks.
The primary efficacy endpoint, the change in HbA1c from baseline to week 26, was met. Canagliflozin demonstrated a significantly greater reduction in HbA1c compared to placebo, with a difference in least-squares means of −0.76% (95% CI, −1.25% to −0.27%; P = 0.002). Consequently, a significantly greater proportion of participants in the canagliflozin group achieved an HbA1c level below 6.5% compared to the placebo group (36.3% vs. 14.0%; difference, 22.3 percentage points [CI, 10.5 to 34.1 percentage points]). These improvements in glycemic control, including significantly improved fasting plasma glucose levels, were maintained through week 52 of the study.
The safety profile of canagliflozin was consistent with that observed in the adult type 2 diabetes mellitus (T2DM) population. Treatment-emergent adverse events (AEs) occurred in 77.4% of the canagliflozin group and 74.7% of the placebo group, with serious AEs reported in 9.5% and 5.7%, respectively. The incidence of hypoglycemia was similar between the groups (11.9% for canagliflozin vs. 10.3% for placebo), with no severe hypoglycemic events reported in the canagliflozin arm. Common AEs included headache, nasopharyngitis, urinary tract infection, and vomiting.
Link to the article: https://www.acpjournals.org/doi/10.7326/ANNALS-24-04017
References Nadgir, U., Ali, S. R., Gogate, J., Shaw, W., Antunes, J., & Fonseca, S. (2025). Treatment with canagliflozin versus placebo in children and adolescents with type 2 diabetes: A randomized clinical trial. Annals of Internal Medicine, ANNALS-24-04017. https://doi.org/10.7326/ANNALS-24-04017
