Insulin-plus-Pramlintide Artificial Pancreas in Type 1 Diabetes—Randomized Controlled Trial
Authors: HAIDAR AHMAD , TSOUKAS MICHAEL , SARAH TWARDY , STRAUSS NATALIA , YALE JEAN FRANCOIS , RUTKOWSKI JOANNA , BOSSY ANNE , PYTKA EVELYNE , NGUYEN HIEU T. , LEGAULT LAURENT 
Published: June 2018

We conducted a randomized crossover comparison between i) dual-hormone, rapid insulin and amylin (Pramlintide), artificial pancreas (DAP), ii) regular insulin (Humulin R) and amylin artificial pancreas (R-DAP), and iii) rapid insulin-alone artificial pancreas (AP) in 12 adults with type 1 diabetes. Insulin and amylin were delivered simultaneously, in a basal-bolus manner, using a novel dosing algorithm, with a fixed ratio (6 µg/u), mimicking a co-formulation. Participants were admitted three times for 24 hours and ingested three meals and a bedtime snack. Prior to closed-loop study, amylin was delivered for two weeks, and basal rates and carb ratios were optimized. Over the 24-hour study, DAP increased time spent in target range [3.9-10.0 mmol/L] compared to AP from 71% to 85% (P=0.03) and decreased glucose variability (CV) from 34% to 25% (P=0.01), without increasing the risk of hypoglycemia (P=NS). Overnight, DAP and AP achieved high and similar time in tight target range [3.9-7.8 mmol/L; 77%, 71%, P=NS]. Moderate nausea was reported by two participants (16%) on DAP compared to 0 (0%) on AP. There was no benefits associated with R-DAP compared to AP during day or night period. We conclude that a dual-hormone artificial pancreas delivering rapid insulin and amylin with fixed ratio improves glucose control and reduces glucose variability compared to insulin-alone, first-generation, artificial pancreas.Table 1.Comparisons between AP, DAP, and R-DAP (mean±SD)OutcomeAPDAPR-DAPP-value DAP vs. APP-value R-DAP vs. APTime spent between 3.9 and 10.0 mmol/L during 24-hour study period (%)71 ± 1985 ± 1072 ± 160.030.86Mean glucose level during 24-hour study period (mmol/L)8.2 ± 1.37.4 ± 1.17.7 ± 0.80.070.38Coefficient of variance during 24-hour study period (%)34 ± 1125 ± 635 ± 80.010.65Time spent between 3.9 and 10.0 mmol/L during daytime period (%)58 ± 2678 ± 1666 ± 210.020.58Mean glucose level during daytime period (mmol/L)9.1 ± 1.97.8 ± 1.58.4 ± 1.50.020.34Time spent between 3.9 and 7.8 mmol/L during overnight period (%)77 ± 2071 ± 2965 ± 190.470.16Mean glucose level during overnight period (mmol/L)6.6 ± 0.96.8 ± 0.96.6 ± 1.20.510.87

Disclosure
A. Haidar: Consultant; Self; Eli Lilly and Company. Research Support; Self; AgaMatrix, Medtronic MiniMed, Inc. M. Tsoukas: Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. S. Twardy: None. N. Strauss: None. J. Yale: Advisory Panel; Self; Medtronic, Abbott. Speaker's Bureau; Self; Abbott. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Takeda Canada Inc.. Speaker's Bureau; Self; Takeda Canada Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc., Bayer AG. Research Support; Self; Mylan, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Sanofi. J. Rutkowski: None. A. Bossy: Other Relationship; Self; Insulet Corporation, Medtronic. E. Pytka: Consultant; Self; Animas Corporation. H.T. Nguyen: None. L. Legault: Advisory Panel; Self; Insulet Corporation. Research Support; Self; Merck & Co., Inc., Sanofi. Advisory Panel; Self; Medtronic. Other Relationship; Self; Eli Lilly and Company.