Safety, Growth, and Development After Dapagliflozin or Saxagliptin in Children With Type 2 Diabetes (T2NOW Follow-Up).

Abstract

The T2NOW trial of dapagliflozin or saxagliptin vs placebo in pediatric patients with type 2 diabetes (T2D) demonstrated promising efficacy data for dapagliflozin and did not raise any safety concerns over 52 weeks. This work aimed to assess long-term effects of prior dapagliflozin/saxagliptin administration on safety, growth, and development. A multicenter, randomized, double-blind phase 3 trial (T2NOW) was conducted among 210 children with T2D aged 10 to 17 years, followed for up to 1 year after treatment. Participants were previously treated with once-daily dapagliflozin (5, 10 mg), saxagliptin (2.5, 5 mg), or placebo as an add-on to diet, exercise, metformin, and/or insulin for 52 weeks, plus a 52-week nontreatment follow-up period. Main outcome measures included change in height, weight, body mass index (BMI), Tanner staging, growth and maturation markers, bone biomarkers, and adverse events (AEs) from baseline to week 104. As expected in a pediatric population, mean height and weight slightly increased from baseline to week 104. BMI remained generally stable; changes were similar across treatment groups. Sexual maturation progressed normally to week 104, with similar shifts between Tanner stages and changes in growth and maturation markers and bone biomarkers across groups. The proportion of patients reporting 1 or more AEs during the nontreatment follow-up period was similar across groups previously treated with dapagliflozin (18.5%) or saxagliptin (15.9%) compared to placebo (21.1%). No deaths occurred. Prior treatment with dapagliflozin or saxagliptin for 52 weeks did not raise any safety concerns relating to height, weight, BMI, Tanner staging, growth and maturation markers, bone biomarkers, or AEs for up to 52 weeks following treatment discontinuation in pediatric patients with T2D.