Original Investigation 

September 7, 2022

Bihormonal Artificial Pancreas With Closed-Loop Glucose Control vs Current Diabetes Care After Total Pancreatectomy: A Randomized Clinical Trial

Charlotte L. van Veldhuisen, Anouk E. J. Latenstein, Helga Blauw, et al

JAMA Surg. Published online September 7, 2022. doi:10.1001/jamasurg.2022.3702

Key Points

Question  What is the efficacy and safety of the novel bihormonal artificial pancreas (BIHAP) in patients after total pancreatectomy?

Findings  This randomized crossover clinical trial compared treatment with a portable, fully automated, European Commission–marked BIHAP with current diabetes care in 12 outpatients after total pancreatectomy. BIHAP was found to increase time in euglycemia (78.30% vs 57.38%) and reduce time in hypoglycemia.

Meaning  In this study, bihormonal artificial pancreas treatment improved glucose regulation in patients with insulin dependent diabetes after total pancreatectomy; future, large, pragmatic randomized trials should assess the long-term effectiveness and safety of the BIHAP, including the effect on patient quality of life.

Abstract

Importance  Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking.

Objective  To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy.

Design, Setting, and Participants  This randomized crossover clinical trial compared the fully closed-loop BIHAP with current diabetes care (ie, insulin pump or pen therapy) in 12 adult outpatients after total pancreatectomy. Patients were recruited between August 21 and November 16, 2020. This first-in-patient study began with a feasibility phase in 2 patients. Subsequently, 12 patients were randomly assigned to 7-day treatment with the BIHAP (preceded by a 5-day training period) followed by 7-day treatment with current diabetes care, or the same treatments in reverse order. Statistical analysis was by Wilcoxon signed rank and Mann-Whitney U tests, with significance set at a 2-sided P < .05.

Main Outcomes and Measures  The primary outcome was the percentage of time spent in euglycemia (70-180 mg/dL [3.9-10 mmol/L]) as assessed by continuous glucose monitoring.

Results  In total, 12 patients (7 men and 3 women; median [IQR] age, 62.5 [43.1-74.0] years) were randomly assigned, of whom 3 did not complete the BIHAP phase and 1 was replaced. The time spent in euglycemia was significantly higher during treatment with the BIHAP (median, 78.30%; IQR, 71.05%-82.61%) than current diabetes care (median, 57.38%; IQR, 52.38%-81.35%; P = .03). In addition, the time spent in hypoglycemia (<70 mg/dL [3.9 mmol/L]) was lower with the BIHAP (median, 0.00% [IQR, 0.00%-0.07%] vs 1.61% [IQR, 0.80%-3.81%]; P = .004). No serious adverse events occurred.

Conclusions and Relevance  Patients using the BIHAP after total pancreatectomy experienced an increased percentage of time in euglycemia and a reduced percentage of time in hypoglycemia compared with current diabetes care, without apparent safety risks. Larger randomized trials, including longer periods of treatment and an assessment of quality of life, should confirm these findings.

Trial Registration  trialregister.nl Identifier: NL8871