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.

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.

• Authors: Torben Biester, Ido Muller, Thekla von dem Berge, Eran Atlas, Revital Nimri, Moshe Phillip, Tadej Battelino, Natasa Bratina, Klemen Dovc, Markus F Scheerer, Olga Kordonouri, Thomas Danne
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 23 Issue 2 Pg. 599-608 (02 2021) ISSN: 1463-1326 [Electronic] England
• PMID: 33217117 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Benzhydryl Compounds
• Blood Glucose
• Glucosides
• Glycated Hemoglobin A
• Hypoglycemic Agents
• dapagliflozin

Topics

• Adolescent
• Benzhydryl Compounds (therapeutic use)
• Blood Glucose
• Diabetes Mellitus, Type 1 (drug therapy)
• Double-Blind Method
• Glucosides (therapeutic use)
• Glycated Hemoglobin
• Humans
• Hypoglycemic Agents (therapeutic use)
• Treatment Outcome
• Young Adult