Automated Basal Insulin Delivery Versus Multiple Daily Injections in Type 1 diabetes: Results from a Randomized Parallel Controlled Trial

Johan Henrik Jendle^1*Satish Garg²Charles Thivolet³Ruth Weinstock⁴Irl Hirsch⁵Mark L Evans⁶Kurt Griffin⁷Athena Philis-Tsimikas⁸Benjamin John Wheeler⁹Mark Kipnes¹⁰Anders Carlson¹¹Bruce Buckingham¹²Anuj Bhargava¹³Bruce Bode¹⁴Margaret Lawson¹⁵Amy Criego¹¹Janet McGill¹⁶John "Chip" H. Reed¹⁷Gnanagurudasan Prakasam¹⁸George Grunberger¹⁹Angela Girelli²⁰María Asunción Martinez-Brocca²¹Mark Christiansen²²Martin De Bock²³Yogish Kudva²⁴Scott W Lee²⁵Fang Niu²⁵Caroline Yovanovich²⁵John Shin²⁵Toni Cordero²⁵Jennifer McVean²⁵Robert Vigersky²⁵

• ¹School of Medicine, Department of Medical Sciences, Örebro University, Örebro, Sweden
• ²Barbara Davis Center for Childhood Diabetes, Aurora, Colorado, United States
• ³HCL- Diab-eCare, Lyon, France
• ⁴SUNY Upstate Medical University, Syracuse, New York, United States
• ⁵University of Washington Medical Center, Seattle, Washington, United States
• ⁶Institute of Metabolic Science and Dept of Medicine, University of Cambridge, Cambridge, United Kingdom
• ⁷Sanford Research Center, Sioux Falls, South Dakota, United States
• ⁸Scripps Clinical Research, La Jolla, California, United States
• ⁹Health New Zealand - Southern, Dunedin, New Zealand
• ¹⁰Diabetes and Glandular Disease Clinic, P.A., San Antonio, Texas, United States
• ¹¹Park Nicollet International Diabetes Center/ Health Partners Institute, Minneapolis, Minnesota, United States
• ¹²Stanford University School of Medicine, Stanford, California, United States
• ¹³Iowa Diabetes Research, West Des Moines, Iowa, United States
• ¹⁴Atlanta Diabetes Associates, Atlanta, Georgia, United States
• ¹⁵Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
• ¹⁶Washington University - Saint Louis, St. Louis, Missouri, United States
• ¹⁷Endocrine Research Solutions, Roswell, Georgia, United States
• ¹⁸Sutter Children’s Center and Sutter Medical Group, Sacramento, California, United States
• ¹⁹Grunberger Diabetes and Endocrinology, Bloomfield Hills, Michigan, United States
• ²⁰Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy
• ²¹Hospital Universitario Virgen Macarena, Seville, Spain
• ²²Diablo Diabetes Center, Walnut Creek, California, United States
• ²³New Zealand Clinical Research, Christchurch, New Zealand
• ²⁴Mayo Clinic Rochester, Rochester, Minnesota, United States
• ²⁵Medtronic Diabetes, Northridge, California, United States

Introduction: This study evaluated 6-month effectiveness and safety of automated insulin delivery (AID) in comparison with multiple daily injections (MDI) in pediatric and adult type 1 diabetes (T1D). Materials and Methods: Individuals with T1D, aged 2-80 years, were enrolled across 32 international centers (in the United States, Europe, Canada and New Zealand) and randomized 1:1 to AID intervention (MiniMed™ 670G or 770G system) or MDI with or without continuous glucose monitoring. Primary endpoints were change in mean A1C for participants with a baseline A1C >8.0% (Group 1) and percentage of time spent below 70mg/dL (%TBR <70mg/dL [<3.9mmol/L]) for participants with baseline A1C ≤8.0% (Group 2), to show superiority of AID intervention versus MDI. Safety endpoints including rates of severe hypoglycemia and diabetic ketoacidosis (DKA) and difference in diabetes treatment satisfaction score were assessed. Results: For Group 1, N=56 participants (aged 29.4±17.0 years) were randomized to AID intervention and N=54 participants (aged 36.8±19.6 years) were randomized to MDI. For Group 2, N=73 (aged 37.4±21.0 years) and N=69 (aged 39.2±19.3 years), respectively, were randomized to AID and MDI. Change in A1C (mean [95% CI] difference of -0.7% [-1.1, -0.3], P=0.0002) and difference in %TBR <70mg/dL (4.8% [-6.4, -3.1], P<0.001) favored AID intervention versus MDI. Rates of severe hypoglycemia (AID: 1.82/100 patient-years) and DKA (MDI: 3.52/100 patient-years) were low and met pre-established success criteria for safety. Discussion: This large, international, multi-center randomized controlled trial demonstrates safety of the MiniMedTM 670G/770G systems. AID significantly improved A1C and time spent in hypoglycemia when compared with MDI, in both youth and adults living with T1D.