Optimizing Basal-Bolus Therapy in T2D—A Randomized Controlled Trial Comparing Bolus Insulin Delivery Using an Insulin Patch vs. an Insulin Pen

Abstract

This multicenter RCT compared clinical, subject-reported, and safety outcomes in T2D subjects on basal insulin (A1C 7.5-11%) initiating mealtime insulin with a wearable bolus insulin delivery patch (Patch, Calibra Medical) vs. an insulin pen (Pen, NovoLog FlexPen®). The Patch was applied at least every 3 days and delivered subcutaneous bolus insulin in 2-U increments per manual click. T2D adults (N=278, age: 59.2 y, duration: 15 y), were randomized to Patch (n=139) or Pen (n=139). Baseline glargine dose was divided 1:1, basal:bolus. Using a pattern-control logbook, subjects adjusted basal and bolus insulin weekly based on fasting and pre-meal glucose targets. Change in A1C (%) from baseline to Week 24 (primary endpoint) for Patch was noninferior (p<.0001) to Pen (LS mean change ± SE: Patch, −1.69 ± 0.vs. Pen, −1.60 ± 0.08) and this reduction was significant (p<.0001) in both groups. A1C improvement was maintained at 44 weeks (Fig). There were no significant differences in adverse events, including hypoglycemia (3 severe episodes/group). There were significantly greater improvements in subject-reported outcomes for Patch vs. Pen. In conclusion, bolus insulin delivered by Patch or Pen along with an algorithm-based weekly insulin dose titration significantly improved A1C levels in subjects with T2D, with improved patient experience and a preference for Patch. Disclosure R.M. Bergenstal: Research Support; Self; Johnson & Johnson Services, Inc.. Consultant; Self; Johnson & Johnson Services, Inc.. Research Support; Self; Abbott. Advisory Panel; Self; Abbott. Research Support; Self; Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Takeda Pharmaceuticals U.S.A., Inc., Dexcom, Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. Research Support; Self; Eli Lilly and Company, Sanofi. Advisory Panel; Self; Sanofi, Roche Pharma. Research Support; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Medtronic. Consultant; Self; Medtronic. Research Support; Self; Hygieia. Advisory Panel; Self; Hygieia, Glooko, Inc.. Research Support; Self; JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases. M. Peyrot: Consultant; Self; Calibra Medical, Eli Lilly and Company, Novo Nordisk Inc.. Research Support; Spouse/Partner; Eli Lilly and Company, Novo Nordisk Inc. D.M. Dreon: Employee; Self; Calibra Medical. V. Aroda: Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc., AstraZeneca, Calibra Medical, Eisai Inc., Sanofi. Consultant; Self; Sanofi. Research Support; Self; Theracos, Inc.. Employee; Spouse/Partner; Merck & Co., Inc.. Other Relationship; Self; American Diabetes Association. Consultant; Self; ADOCIA. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. R.L. Brazg: Research Support; Self; Abbott, Calibra Medical, Dexcom, Inc., Eli Lilly and Company, GlucoMe, Novo Nordisk Inc., Medtronic. Speaker's Bureau; Self; Medtronic. Research Support; Self; Sanofi-Aventis, Senseonics, Gan & Lee Pharmaceuticals, Gelesis. J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson & Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc. M.L. Johnson: Research Support; Self; Calibra Medical, Medtronic, Sanofi, Novo Nordisk Inc., Abbott, POPS! Diabetes Care, National Institute of Diabetes and Digestive and Kidney Diseases, Dexcom, Inc., Hygieia, JDRF. D.C. Klonoff: Consultant; Self; Ascensia Diabetes Care, Lifecare, Intarcia Therapeutics, Inc., Voluntis USA, Novo Nordisk Inc., Onduo, Trividia Health, Inc., American Diabetes Association, The Endocrine Society, American Association of Diabetes Educators. D.F. Kruger: Research Support; Self; Dexcom, Inc.. Speaker's Bureau; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Intarcia Therapeutics, Inc., Abbott. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; JAEB Center For Health Research. Consultant; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Hygieia, Lexicon Pharmaceuticals, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Valeritas, Inc., Insulet Corporation. Consultant; Self; Insulet Corporation. Research Support; Self; Insulet Corporation. Consultant; Self; Merck & Co., Inc. S. Ramtoola: Other Relationship; Self; Janssen Research & Development. Stock/Shareholder; Self; Novo Nordisk A/S, Johnson & Johnson, Eli Lilly and Company. J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. P. Serusclat: Board Member; Self; Novo Nordisk A/S, Medtronic, Abbott. Research Support; Self; Novo Nordisk A/S, Eli Lilly and Company, Sanofi. R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases. R.G. Naik: Other Relationship; Self; LifeScan, Inc.. D.M. Shearer: None. V. Zraick: Other Relationship; Self; Calibra Medical. B.L. Levy: Employee; Self; LifeScan, Inc..