Torben Biester1, Ido Muller2, Thekla von dem Berge1, Eran Atlas2, Revital Nimri3, Moshe Phillip3,4, Tadej Battelino5,6, Natasa Bratina5,6, Klemen Dovc5,6, Markus F Scheerer7, Olga Kordonouri1, Thomas Danne1. 1. Diabetes Centre for Children and Adolescents, Kinder und Jugendkrankenhaus, Auf der Bult, Hannover, Germany. 2. DreaMed Diabetes Ltd, Petah Tikva, Israel. 3. The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Centre for Childhood Diabetes, Schneider Children's Medical Centre of Israel, Petah Tikva, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Department of Paediatric Endocrinology, Diabetes and Metabolic Diseases, UMC - University Children's Hospital, Ljubljana, Slovenia. 6. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. 7. AstraZeneca, Wedel, Germany.
Abstract
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.
RCT Entities:
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-obesepersons 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.
Authors: Stuart A Weinzimer; Ryan J Bailey; Richard M Bergenstal; Revital Nimri; Roy W Beck; Desmond Schatz; Louise Ambler-Osborn; Darja Smigoc Schweiger; Thekla von dem Berge; Judy Sibayan; Mary L Johnson; Peter Calhoun; Moshe Phillip Journal: Diabetes Technol Ther Date: 2022-04-28 Impact factor: 7.337