title: Diurnal Glycemic Patterns during an 8-Week Open-Label Proof-of-Concept Trial of Empagliflozin in Type 1 Diabetes.
abstract: BACKGROUND
  We recently reported improved glycemic control with reduced insulin dose in subjects with type 1 diabetes treated with the sodium glucose co-transporter-2 inhibitor empagliflozin. To further characterize the effects, we analyzed diurnal glycemic patterns by continuous glucose monitoring (CGM).
  
  
  METHODS
  In an 8-week single-arm open-label pilot study of empagliflozin, we compared ambulatory glucose profiles produced from CGM data during 2-week intervals in a placebo run-in baseline period, end-of-treatment, and post-treatment. Change in glycemic exposure was evaluated by area under the median curve according to time of day (AUCTOTAL 12:00am-11:55pm; AUCDAY 7:05am-10:55pm, AUCNIGHT 11:00pm-7:00am), as well as glycemic variability, glycemic stability and time-in-target (≥70 to ≤140mg/dL).
  
  
  RESULTS
  The 40 patients (26 on insulin pump) were aged 24±5 years and BMI 24.5±3.2 kg/m2. Consistent with the observed HbA1c decrease (8.0±0.9% to 7.6±0.9%, p<0.0001), normalized AUCTOTAL CGM decreased from 153.7±25.4 to 149.0±30.2mg/dL∙h at end-of-treatment (p = 0.31), and significantly increased post-treatment (164.1±29.5mg/dL∙h, p = 0.02). The numerical decrease in normalized AUCNIGHT (152.0±36.6 to 141.9±34.4mg/dL∙h, p = 0.13) exceeded AUCDAY (154.5±24.5 to 152.6±30.4mg/dL∙h, p = 0.65). Trends toward lower glycemic variability (83.1±18.9 to 75.6±28.6mg/dL, p = 0.06) and little change in glycemic stability (10.8±3.6 to 10.3±4.5mg/dL/h, p = 0.51) were observed. When empagliflozin was discontinued, these worsened relative to baseline (89.3±19.3mg/dL, p = 0.04 and 11.8±3.7mg/dL/hr, p = 0.08). Time-in-target numerically increased (40.2±11.9 to 43.1±13.5%, p = 0.69) at end-of-treatment but reversed post-treatment. Findings were similar on stratification of pump and MDI subjects.
  
  
  CONCLUSIONS
  We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01392560.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Perkins
authors.affiliation: Department of Medicine, Division of Nephrology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
authors.affiliation: Boehringer Ingelheim Canada Ltd./Ltée, Burlington, ON, Canada.
authors.forename: Nima
authors.initials: N
authors.lastname: Soleymanlou
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Partridge
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
authors.forename: Holly
authors.initials: H
authors.lastname: Tschirhart
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: WHO Collaborating Center, Minneapolis, Minnesota, United States of America.
authors.forename: Roger
authors.initials: R
authors.lastname: Mazze
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States of America.
authors.forename: Nora
authors.initials: N
authors.lastname: Fagan
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaspers
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
authors.affiliation: Boehringer Ingelheim Norway K.S, Asker, Norway.
authors.forename: Odd Erik
authors.initials: OE
authors.lastname: Johansen
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C570240:empagliflozin