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Dapagliflozin Approved by FDA to Improve Glycemic Control in Children, Adolescents with T2D


Among youth aged 10 to 17 years with uncontrolled hyperglycemia dapagliflozin led to a statistically significant reduction in A1c vs placebo in the T2NOW phase 3 clinical trial.

The FDA has approved dapagliflozin (Farxiga; AstraZeneca) for youths aged 10 years and older with uncontrolled type 2 diabetes (T2D) to improve glycemic control, according to a press release from AstraZeneca.1

The once-daily, oral, sodium-glucose cotransporter 2 (SGLT2) inhibitor was approved for use in this younger population based on data from the pediatric T2NOW phase 3 trial (NCT03199053), which demonstrated a significant reduction in A1c in patients treated with dapagliflozin compared to placebo, on a background of metformin, insulin, or both.2

Dapagliflozin Approved by FDA to Improve Glycemic Control in Children, Adolescents with T2D/ image credit FDA approval stamp: ©Waldenmarus/stock.adobe.com

Dapagliflozin was approved in 2012 as a first-in-class SGLT2 inhibitor for the treatment of T2D in adults as an adjunct to diet and exercise.1

T2NOW, described as one of the largest pediatric T2D phase 3 trials to date,1 was designed to evaluate the safety and efficacy of the SGLT2 inhibitor as add-on treatment in children and adolescents with T2D with persistent hyperglycemia.2 T2NOW was 26-week study with a 26-week extension among participants aged 10 to 17 years with uncontrolled T2D (A1c 6.5% to 10.5%) despite treatment with metformin, insulin, or both. Study participants were assigned randomly 1:1:1 to 5 mg of dapagliflozin (n = 81), 2.5 mg of saxagliptin (Onglyza; AstraZeneca) (n = 88), or placebo (n = 76).2

Participants in the dapagliflozin and saxagliptin treatment groups with A1c of 7% or greater at week 12 were then randomly assigned 1:1 at week 14 to either continue the original dose of active treatment drug or to titrate to a higher dose (10 mg of dapagliflozin or 5 mg of saxagliptin). The trial’s primary endpoint was change in A1c after 26 weeks for dapagliflozin or saxagliptin vs placebo. The findings were published in The New England Journal of Medicine.2

T2NOW results

The adjusted mean change in A1c at 26 weeks was for dapagliflozin was –1.03% (95% CI, –1.57 to –0.49; P < .001) and −0.44% (95% CI, −0.93 to 0.05; [P = .078]) for saxagliptin compared with placebo. Adverse events and serious adverse events occurred in 72.8% and 8.6%, respectively, of participants who received dapagliflozin, 69.3% and 8.0% of patients who received saxagliptin, and 71.1% and 6.6% of participants who received placebo.2

Investigators reported similar incidence of severe hypoglycemia in the active treatment groups (4.9% for dapagliflozin, 4.5% for saxagliptin) and a slightly higher incidence (7.9%) in placebo-treated participants.2 The most common adverse event (AE) was nonserious headache, more likely in the dapagliflozin group (14.8%) compared with placebo (5.3%). Overall AEs were reported as mild; none were deemed serious; and the safety profile was consistent with those observed in adults with T2D. No AEs led to trial discontinuation.2

All T2NOW secondary endpoints achieved statistical significance as well and included change in fasting plasma glucose and proportion of patients (A1c ≥7% at baseline) achieving A1c <7.0% after 26 weeks.1

The prevalence of T2D in children and adolescents is increasing globally, with one estimate suggesting nearly 30 000 people younger than age 20 years live with the metabolic disorder in the US.3 The Centers for Disease Control and Prevention estimate that 5300 new cases are diagnosed each year in the age group.4 With early onset of T2D, younger individuals are at risk for both faster progression of the disease as well as earlier onset of diabetes-related complications, AstraZeneca pointed out.1

"The prevalence of type-2 diabetes continues to rise in children and adolescents, yet oral treatment options have remained limited for this population," Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, AstraZeneca, said in the press statement.1 "Today’s approval represents an important milestone for pediatric patients living with type-2 diabetes in the US, extending this medicine’s potential benefits to even more patients facing high unmet needs and reinforcing AstraZeneca’s commitment to delivering innovative treatments across cardiovascular, renal and metabolic diseases.”1

  1. Farxiga approved in the US for the treatment of paediatric type-2 diabetes. AstraZeneca. Press release. June 12, 2024. Accessed June 17, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/farxiga-approved-in-the-us-for-the-treatment-of-paediatric-type-2-diabetes.html 
  2. Shehadeh N, Barrett T, Galassetti P, et al. Dapagliflozin or saxagliptin in pediatric type 2 diabetes. NEJM Evidence. 2023;2(12). doi:10.1056/EVIDoa2300210
  3. Wu H, Patterson C, Zhang X, et al. Worldwide estimates of incidence of type 2 diabetes in children and adolescents in 2021. Diabetes Res Clin Pract. 2022;185:109785. doi:10.1016/j.diabres.2022.109785
  4. Tönnies T, Brinks R, Isom S, et al. Projections of type 1 and type 2 diabetes burden in the US population aged <20 years through 2060: The SEARCH for Diabetes in Youth Study. Diabetes Care. 2023;46(2):313-320. doi:10.2337/dc22-0945

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