Add-on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study

Aim: To investigate the effect of the sodium-glucose co-transporter-2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions. Materials and Methods: For this single-centre, double-blind, randomized, placebo-controlled, cross-over trial, non-obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9-10 mmol/L). For safety evaluation, ss-hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured. Results: Fifteen adolescents (aged 15.4 +/- 1.6 years, diabetes duration 10.0 +/- 3.4 years, HbA1c 8.4% +/- 0.9% [67.7 +/- 10.1 mmol/mol]) and 15 young adults (aged 18.7 +/- 0.8 years; diabetes duration 12.5 +/- 3.6 years; HbA1c 8.3% +/- 0.9% [68.5 +/- 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% +/- 6% vs. 50% +/- 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 +/- 0.7 vs. 7.3 +/- 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% +/- 6.0% vs 3.1% +/- 5.2%; P = .75). Urinary glucose excretion was increased 3-fold using dapagliflozin (149 +/- 42 vs. 49 +/- 23 g/24 hours) with a total insulin reduction of 22% (39.7 +/- 12.7 vs. 30.6 +/- 10.4 U; P = .004). No abnormal elevated BHB values were observed. Conclusions: In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.