Susanne Famulla1, Thomas R Pieber2, Jens Eilbracht3, Dietmar Neubacher3, Nima Soleymanlou4, Hans J Woerle5, Uli C Broedl5, Stefan Kaspers5. 1. 1 Profil GmbH , Neuss, Germany . 2. 2 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz , Graz, Austria . 3. 3 Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach, Germany . 4. 4 Boehringer Ingelheim Canada Ltd./Ltee , Burlington, Canada . 5. 5 Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim, Germany .
Abstract
BACKGROUND: We evaluated the effect of empagliflozin as adjunct to insulin on 24-h glucose exposure and variability in patients with type 1 diabetes. METHODS:Patients (N = 75) with HbA1c ≥7.5% to ≤10.5% were randomized to receive empagliflozin 2.5 mg, empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily as adjunct to insulin for 4 weeks. Insulin dose was to be kept as stable as possible during week 1 of treatment and was freely adjustable thereafter. Markers of glucose exposure and variability were assessed from 7-day blinded continuous glucose monitoring intervals. This study is completed ( ClinicalTrials.gov NCT01969747). RESULTS:Empagliflozin reduced hourly mean glucose area under the median curve over 24 h versus placebo within week 1 (adjusted mean differences: -12.2 mg/dL·h [95% confidence interval -23.9 to -0.5], -30.2 mg/dL·h [-42.2 to -18.2], and -33.0 mg/dL·h [-44.8 to -21.1] with empagliflozin 2.5, 10, and 25 mg, respectively; all P < 0.05) and increased time in glucose target range (>70 to ≤180 mg/dL). Results were sustained to week 4 with empagliflozin 25 mg. All empagliflozin doses significantly reduced glucose variability (interquartile range and mean amplitude of glucose excursions) versus placebo at weeks 1 and 4. Except for small increases in hours per day with glucose ≤70 mg/dL during the stable insulin period, empagliflozin did not increase time in hypoglycemia compared with placebo. CONCLUSIONS: In patients with type 1 diabetes, empagliflozin as adjunct to insulin decreased glucose exposure and variability and increased time in glucose target range.
RCT Entities:
BACKGROUND: We evaluated the effect of empagliflozin as adjunct to insulin on 24-h glucose exposure and variability in patients with type 1 diabetes. METHODS:Patients (N = 75) with HbA1c ≥7.5% to ≤10.5% were randomized to receive empagliflozin 2.5 mg, empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily as adjunct to insulin for 4 weeks. Insulin dose was to be kept as stable as possible during week 1 of treatment and was freely adjustable thereafter. Markers of glucose exposure and variability were assessed from 7-day blinded continuous glucose monitoring intervals. This study is completed ( ClinicalTrials.gov NCT01969747). RESULTS:Empagliflozin reduced hourly mean glucose area under the median curve over 24 h versus placebo within week 1 (adjusted mean differences: -12.2 mg/dL·h [95% confidence interval -23.9 to -0.5], -30.2 mg/dL·h [-42.2 to -18.2], and -33.0 mg/dL·h [-44.8 to -21.1] with empagliflozin 2.5, 10, and 25 mg, respectively; all P < 0.05) and increased time in glucose target range (>70 to ≤180 mg/dL). Results were sustained to week 4 with empagliflozin 25 mg. All empagliflozin doses significantly reduced glucose variability (interquartile range and mean amplitude of glucose excursions) versus placebo at weeks 1 and 4. Except for small increases in hours per day with glucose ≤70 mg/dL during the stable insulin period, empagliflozin did not increase time in hypoglycemia compared with placebo. CONCLUSIONS: In patients with type 1 diabetes, empagliflozin as adjunct to insulin decreased glucose exposure and variability and increased time in glucose target range.
Authors: Tadej Battelino; Thomas Danne; Richard M Bergenstal; Stephanie A Amiel; Roy Beck; Torben Biester; Emanuele Bosi; Bruce A Buckingham; William T Cefalu; Kelly L Close; Claudio Cobelli; Eyal Dassau; J Hans DeVries; Kim C Donaghue; Klemen Dovc; Francis J Doyle; Satish Garg; George Grunberger; Simon Heller; Lutz Heinemann; Irl B Hirsch; Roman Hovorka; Weiping Jia; Olga Kordonouri; Boris Kovatchev; Aaron Kowalski; Lori Laffel; Brian Levine; Alexander Mayorov; Chantal Mathieu; Helen R Murphy; Revital Nimri; Kirsten Nørgaard; Christopher G Parkin; Eric Renard; David Rodbard; Banshi Saboo; Desmond Schatz; Keaton Stoner; Tatsuiko Urakami; Stuart A Weinzimer; Moshe Phillip Journal: Diabetes Care Date: 2019-06-08 Impact factor: 19.112