title: Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.
abstract: The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity.
  
  
  
  We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2-11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220.
  
  
  
  We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7-1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study.
  
  
  
  Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas.
  
  
  
  National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: Firas H
authors.initials: FH
authors.lastname: El-Khatib
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Balliro
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Mallory A
authors.initials: MA
authors.lastname: Hillard
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Magyar
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Laya
authors.initials: L
authors.lastname: Ekhlaspour
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Manasi
authors.initials: M
authors.lastname: Sinha
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Debbie
authors.initials: D
authors.lastname: Mondesir
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Aryan
authors.initials: A
authors.lastname: Esmaeili
authors.affiliation: Center for Clinical and Translational Science and the Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Hartigan
authors.affiliation: Center for Clinical and Translational Science and the Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thompson
authors.affiliation: Center for Clinical and Translational Science and the Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Malkani
authors.affiliation: Center for Clinical and Translational Science and the Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Lock
authors.affiliation: Center for Clinical and Translational Science and the Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Harlan
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Clinton
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Frank
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Darrell M
authors.initials: DM
authors.lastname: Wilson
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: DeSalvo
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Norlander
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Trang
authors.initials: T
authors.lastname: Ly
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Buckingham
authors.affiliation: Diabetes Care Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Diner
authors.affiliation: Diabetes Care Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: Milana
authors.initials: M
authors.lastname: Dezube
authors.affiliation: Diabetes Care Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Young
authors.affiliation: Diabetes Care Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: April
authors.initials: A
authors.lastname: Goley
authors.affiliation: Diabetes Care Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: M Sue
authors.initials: MS
authors.lastname: Kirkman
authors.affiliation: Diabetes Care Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: Rajendranath R
authors.initials: RR
authors.lastname: Selagamsetty
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Damiano
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. Electronic address: sjrussell@mgh.harvard.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Russell
mesh_terms: D000328:Adult; D001701:Bionics; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000627:therapeutic use; D006728:Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009325:Nausea / Q000139:chemically induced; D019397:Pancreas, Artificial; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon