A novel dual-hormone artificial pancreas system that delivers both rapid insulin and pramlintide was found to improve glucose control compared with a rapid insulin-alone system, without increasing the risk for hypoglycemia in adults with type 1 diabetes (T1D), according to study results published in Diabetes Care.
The artificial pancreas system is intended to automate insulin pump delivery in T1D based on glucose sensor reading and a dosing algorithm. Pramlintide, an amylin analog that can be injected at mealtimes, has been added to some artificial pancreas systems to potentially delay gastric emptying, suppress glucagon secretion, and increase satiety.
In the current study (ClinicalTrials.gov Identifier: NCT02814123), the researchers compared an artificial pancreas system that delivers pramlintide with either rapid-acting or regular insulin with an insulin-alone artificial pancreas in adults with T1D. The primary outcome was time spent in range (70-180 mg/dL).
The open-label randomized crossover study included adults with T1D enrolled at the Research Institute of McGill University Health Center in Montreal, Canada, from February 2017 to July 2018. All participants had been using an insulin pump for ≥6 months prior to enrollment. The patients were assigned in random order to 1 of 3 study interventions: insulin-alone artificial pancreas, rapid insulin/pramlintide system, or regular insulin/pramlintide system. Each intervention lasted 24 hours, and intervention visits were separated by a median of 14 days.
Mean percentage of time spent in the target range was higher with the rapid insulin/pramlintide artificial pancreas compared with the rapid insulin-alone system (74% vs 84%; P =.0014). In addition, mean glucose was reduced (142.34 to 133.33 mg/dL; P =.0053), as was the percent time spent at >180 mg/dL (22% to 12%; P =.00012), glucose coefficient of variance (from 30.3% to 26.8%, respectively; P =.035), and standard deviation (from 43.24 to 36.04 mg/dL; P =.0053).
On the other hand, there were no benefits associated with the regular insulin/pramlintide system compared with the rapid insulin-alone artificial pancreas for percentage of time spent in range (69% vs 74%, respectively; P =.22), mean glucose, time spent >180 mg/dL, glucose coefficient of variance, or standard deviation.
The benefits of the rapid insulin/pramlintide artificial pancreas were attributed to improved glucose control during the day. During the daytime hours (8 AM-11 PM), the rapid insulin/pramlintide system increased the time in target range compared with the rapid insulin-alone artificial pancreas from 63% to 78% (P =.0004). Mean glucose level was reduced from 156.76 to 142.34 mg/dL (P =.0011), glucose coefficient of variance was reduced from 29.3% to 25.6% (P =.017), and glucose standard deviation was reduced from 45.05 to 36.04 mg/dL (P =.0019).
With the use of rapid insulin alone, there were 11 hypoglycemic events that required oral treatment (1 per 2.5 days) compared with 12 events with the use of rapid insulin plus pramlintide (1 per 2.3 days) and 18 events with the use of regular insulin plus pramlintide (1 per 1.4 days).
There was no record of severe gastrointestinal adverse effects with any of the 3 systems. In fact, with rapid insulin alone, there were no gastrointestinal symptoms reported for any patients. Use of rapid insulin plus pramlintide was associated with mild (2 patients, 7%) or moderate (3 patients, 11%) gastrointestinal symptoms, whereas with regular insulin plus pramlintide, 1 patient (4%) had mild symptoms, 3 (12%) had moderate, and 2 (8%) had moderate to severe gastrointestinal symptoms.
The researchers acknowledged several study limitations, including that the study was conducted in inpatient settings on a single day, lack of allocation blinding, and use of manual control to operate the artificial pancreas systems.
“Studies with the rapid insulin-and-pramlintide artificial pancreas in free-living outpatient settings are now warranted,” concluded the researchers.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Haidar A, Tsoukas MA, Bernier-Twardy S, et al. A novel dual-hormone insulin-and-pramlintide artificial pancreas for type 1 diabetes: a randomized controlled crossover trial [published online January 23, 2020]. Diabetes Care. doi:10.2337/dc19-1922