TOPLINE:
Canagliflozin, an SGLT2 inhibitor, significantly reduced A1c levels in children and adolescents with type 2 diabetes (T2D) compared with placebo after 26 weeks. More participants who received canagliflozin achieved the A1c goal of less than 6.5% or 7.0% than those who received placebo at week 26.
METHODOLOGY:
- A phase 3 randomized controlled trial was conducted across 104 sites in 10 countries and enrolled 171 participants (aged ≥ 10 years to < 18 years) with T2D and A1c levels between ≥ 6.5% and ≤ 11%.
- Eligible participants had inadequate glycemic control despite following a diet and exercise regimen alone or in combination with receiving stable doses of metformin, insulin, or both.
- Participants were randomly assigned to receive either 100 mg oral canagliflozin (n = 84) or a placebo (n = 87) once daily. At week 13, those with A1c levels ≥ 7% and an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m² were reassigned to either continue 100 mg/d canagliflozin, increase their dose to 300 mg/d, or receive a matching placebo. Participants with A1c levels < 7% continued their original treatment.
- The primary efficacy endpoint was the change in A1c levels from baseline to week 26, and safety assessments included monitoring for adverse events and hypoglycemic events.
- The mean duration of treatment exposure was 337.8 days for the canagliflozin group and 335.0 days for the placebo group.
TAKEAWAY:
- Participants receiving canagliflozin showed a significant reduction in A1c levels at week 26 compared with those receiving placebo (difference in least squares means, -0.76%; P = .002). The results were similar for those who also received metformin, with or without insulin.
- Fasting plasma glucose levels improved significantly from baseline in the canagliflozin group compared with the placebo group at both week 26 and week 52.
- At week 26, a significantly higher proportion of participants receiving canagliflozin than placebo achieved A1c levels below 6.5% (marginal proportions, 36.3% vs 14.0%) or below 7.0% (marginal proportions, 45.7% vs 32.8%), with similar findings noted at week 52.
- Ten participants (11.9%) who received canagliflozin needed rescue medication by week 52 compared with 40 participants (46.0%) who received placebo. Treatment-emergent adverse events occurred in 77.4% of the canagliflozin group and 74.7% of the placebo group, with events such as headache, nasopharyngitis, and urinary tract infection occurring more frequently in the canagliflozin than placebo group.
IN PRACTICE:
“The data from this trial provide support for the use of canagliflozin in the clinical management of T2DM [type 2 diabetes mellitus] in children and adolescents aged 10 years or older,” the authors wrote.
“Canagliflozin, an SGLT2 inhibitor, was recently approved for use in youth with T2D on the basis of Nadgir and colleagues’ clinical trial that demonstrates safety and efficacy in this population,” experts wrote in an accompanying editorial. “[SGLT2] inhibitors offer an oral option for youth not wanting injections. However, the aggressive nature of youth-onset T2D means that combination medical therapy is often necessary.”
SOURCE:
The study was led by Ulhas Nadgir, MD, from Sutter Medical Group in Sacramento, California. It was published online on August 5, 2025, in Annals of Internal Medicine.
LIMITATIONS:
The 52-week length of this study limited the understanding of long-term glycemic control and growth effects. The small number of participants limited the ability to identify safety issues. Differences in the baseline characteristics of the treatment groups mean that some unmeasured factors could have influenced the results.
DISCLOSURES:
The study was funded by Johnson & Johnson, which was involved in the design, data collection, analysis, and publication decisions. Several authors disclosed their employment and stock or stock options: two with Johnson & Johnson; one with Johnson & Johnson International; one with Janssen Research & Development, LLC; and one with Janssen Pharmaceuticals. Payment for writing assistance was provided by Parexel.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.