Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes.

BACKGROUND: Incidence of type 2 diabetes (T2D) in children and adolescents is increasing, but treatment options are limited. METHODS: This was a 26-week, phase 3 trial with a 26-week extension among patients (10 to 17 years of age) with uncontrolled T2D (A1C 6.5 to 10.5%) receiving metformin, insulin, or both. Participants were randomly assigned 1:1:1 to 5 mg of dapagliflozin (N=81), 2.5 mg of saxagliptin (N=88), or placebo (N=76). Patients in active treatment groups with A1C ≥7% at week 12 were further randomly assigned 1:1 at week 14 to continue the dose or up-titrate to a higher dose (10 mg of dapagliflozin or 5 mg of saxagliptin). The primary end point was change in A1C at week 26. Safety was assessed over 52 weeks. RESULTS: At week 26, the difference versus placebo in adjusted mean change in A1C was −1.03 percentage points (95% confidence interval [CI], −1.57 to −0.49; P<0.001) for dapagliflozin and −0.44 percentage points (95% CI, −0.93 to 0.05; P=0.078) for saxagliptin. Adverse events (AEs) and serious AEs occurred in 72.8% and 8.6% of patients receiving dapagliflozin, 69.3% and 8.0% of patients receiving saxagliptin, and 71.1% and 6.6% of patients receiving placebo. Severe hypoglycemia occurred in 4.9%, 4.5%, and 7.9% of patients in each group, respectively. Over 52 weeks, the most common AE was headache (dapagliflozin 14.8%; placebo 5.3%). Most events were mild and none was considered serious or resulted in discontinuation. CONCLUSIONS: Dapagliflozin, but not saxagliptin, showed significant improvement in A1C compared with placebo. Nonserious headaches were more common in participants treated with dapagliflozin than in those receiving placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03199053.)