Orlando, Florida - A dual-hormone, artificial pancreas  delivering rapid insulin and the drug pramlintide improved glucose control and reduced glucose variability in adults with type 1 diabetes (T1D) compared to an insulin-only, first-generation artificial pancreas, according to the study, “Insulin-plus-Pramlintide Artificial Pancreas in Type 1 Diabetes—Randomized Controlled Trial,” presented today at the American Diabetes Association’s®  (ADA’s) 78th Scientific Sessions® at the Orange County Convention Center Convention Center.

Managing T1D can be challenging, and maintaining healthy blood glucose levels is an integral part of preventing diabetes-related complications. Artificial pancreas systems work to automate blood-glucose management using a device that constantly monitors a person’s blood glucose levels and then delivers insulin or a combination of insulin and other blood-glucose-lowering medications to the body.

Pramlintide is a synthetic, injectable analog of amylin, a hormone that is produced by the pancreas and released into the bloodstream after meals to help regulate blood glucose levels. Like insulin, amylin is completely absent in individuals with T1D. Apart from insulin analogs, pramlintide is the only drug to lower blood glucose in people with T1D and approved by the Food and Drug Administration (FDA) since insulin was certified in the early 1920s. Pramlintide was approved by the FDA in March 2005.

This Canadian study was a randomized, crossover comparison of a first-generation, rapid, insulin-only artificial pancreas (AP), and two novel, dual-hormone, artificial pancreas systems: 1) a rapid insulin and amylin (pramlintide) artificial pancreas (DAP), and 2) a regular insulin (Humulin R) and amylin artificial pancreas (R-DAP). The study enrolled 12 adults (7 males and 5 females, average age 43 years) with T1D and an average HbA1c level of 7.6 percent. All participants were studied three times in a clinical research facility for 24 hours (each participant was studied using each of the three artificial pancreas systems). During each 24-hour period, each participant consumed three meals and a bedtime snack. Insulin and amylin were delivered simultaneously in a basal-bolus manner using a dosing algorithm with a fixed ratio, mimicking a co-formulation. 

The results showed that, on average, the DAP system improved the patients’ blood glucose levels more than the AP system. The DAP had a longer timeframe that participants spent in the target blood glucose range of 3.9-10.0 mmol/L (85 percent), compared to the AP system (71 percent; p=.03). The DAP system also decreased glucose variability more (34 percent), compared to the AP system (25 percent; p=.01). Further, the DAP system produced a reduced, mean glucose level of 7.4 mmol/L compared to the AP system’s reduction to 8.2 mmol/L (p=.07), without increasing the risk of hypoglycemia. Overnight, DAP and AP achieved similarly positive rates in the target blood glucose range of 3.9-7.8 mmol/L (77 percent and 71 percent, respectively). However, moderate nausea was reported by two participants using DAP compared to no reports of nausea using AP. There were no benefits associated with R-DAP compared to AP during either the day or night study periods.

“We were expecting some benefits with the insulin-plus-pramlintide artificial pancreas, yet we were impressed by both the extent of improvements and the lack of side effects, considering these benefits were achieved without increasing the risk of dangerous low-glucose levels,” said lead study author Ahmad Haidar, PhD, assistant professor in the department of biomedical engineering, faculty of medicine at McGill University in Montreal, Canada. “This study shows that the first-generation, insulin-only artificial pancreas can be improved by delivering other hormones along with insulin, which will hopefully encourage the development of insulin-plus-pramlintide co-formulations.”

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 were 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.

Author Disclosures:  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.