Canagliflozin may be an option for type 2 diabetes in children and adolescents

The incidence of type 2 diabetes in children and adolescents has increased over the past two decades and is expected to rise further. Children with type 2 diabetes have more rapid beta-cell functional decline compared to adults, as well as accelerated disease progression, earlier onset of complications, and more frequent treatment failure with glucose-lowering treatments. Treatment options for children and adolescents with type 2 diabetes are limited, with guidelines suggesting metformin as first-line therapy in asymptomatic patients, insulin for symptomatic patients with marked hyperglycemia, and some evidence for use of a glucagon-like peptide-1 receptor agonist or sodium–glucose cotransporter-2 (SGLT2) inhibitor in individuals who do not meet glycemic goals with first-line therapy.Canagliflozin, a sodium–glucose cotransporter-2 inhibitor, is approved for the treatment of type 2 diabetes in adults. To examine its safety and efficacy in children and adolescents, US researchers conducted a randomized, double-blind, placebo-controlled, parallel-group study in children (age ≥ 10 years) with type 2 diabetes. Study participants had inadequate glycemic control (glycated hemoglobin [A1C] ≥ 6.5% to ≤11%). They had received a diet and exercise regimen alone for at least four weeks or in combination with a stable dose of metformin monotherapy (≥ 1000 mg/d or maximum tolerable dose), a stable dose of insulin monotherapy, or a combination of metformin plus insulin for at least eight weeks.Individuals were randomly assigned to canagliflozin (100 mg) or placebo once daily.Participants with week 12 readings of 7% or higher for A1C and at least 60 mL/min/1.73 m2 for estimated glomerular filtration rate were randomly assigned again at week 13 to continue with canagliflozin 100 mg once daily (or placebo) or have their dose up-titrated to 300 mg once daily (or placebo). Participants were treated for 52 weeks.The primary end efficacy point was the change in A1C from baseline to week 26 (primary efficacy end point). Safety and tolerability were also examined. Results showed the following:171 participants were randomly assigned to canagliflozin (n=84) or placebo (n=87).At week 26, A1C reduction from baseline was significantly greater with canagliflozin than placebo (difference in least-squares means, -0.76% [95% CI, -1.25% to -0.27%]; p=0.002).The proportion of participants who achieved A1C levels below 6.5% was significantly greater with canagliflozin than placebo (36.3% vs. 14.0%; difference, 22.3 percentage points [CI, 10.5–34.1 percentage points]).Similar results were obtained in the subgroup of participants who received metformin with or without insulin.Treatment-emergent adverse events occurred in 77.4% (canagliflozin) and 74.7% (placebo) of participants. Common adverse events with canagliflozin were similar to those seen in adults (headache, nasopharyngitis, urinary tract infection, vomiting).Serious treatment-emergent adverse events occurred in 9.5% (canagliflozin) and 5.7% (placebo) of participants. Hypoglycemia occurred in 11.9% (canagliflozin) and 10.3% (placebo) of participants. No severe hypoglycemic events occurred with canagliflozin.The authors conclude that based on these study results, canagliflozin significantly improves glycemic control in children and adolescents (age 10–17 years) with type 2 diabetes. It leads to a clinically meaningful reduction in A1C, with a safety profile similar to that seen in adults. The authors note that the main limitations of their trial was the relatively short duration and relatively small sample size.ReferenceNadgir U, Ali SR, Gogate J, et al. Treatment with canagliflozin versus placebo in children and adolescents with type 2 diabetes: a randomized clinical trial. Ann Intern Med 2025. Published August 5, 2025 online ahead of print. (accessed September 9, 2025).

Canagliflozin may be an option for type 2 diabetes in children and adolescents

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