Effects of dapagliflozin on insulin-requirement, glucose excretion and ß-hydroxybutyrate levels are not related to baseline HbA1c in youth with type 1 diabetes.

Published on Nov 1, 2017in Diabetes, Obesity and Metabolism5.9
· DOI :10.1111/DOM.12975
Torben Biester14
Estimated H-index: 14
(Boston Children's Hospital),
Baerbel Aschemeier2
Estimated H-index: 2
(Boston Children's Hospital)
+ 4 AuthorsThomas Danne55
Estimated H-index: 55
(Boston Children's Hospital)
Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. A total of 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into 3 baseline HbA1c categories ( 9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels at 160 to 220 mg/dL. DAPA reduced mean insulin dose by 13.6% ( P  < .0001 by ANOVA) and increased urinary glucose excretion by 610% (143.4 vs 22.4 g/24 h; P  < .0001), both irrespective of baseline HbA1c. Six independent episodes in 6 patients with plasma s-hydroxybutyrate levels between ≥0.6 and <1.0 mmol/L were observed after liquid meal challenges, 5 episodes in the DAPA group and 1 in the placebo group. This study provides a proof-of-concept, irrespective of preexisting HbA1c levels, for adjunct SGLT2-inhibitor therapy in the paediatric age group by lowering insulin dose and increasing glucose excretion.
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