Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial
Open accessAbstract
BACKGROUND: Most patients with type 1 diabetes do not achieve their glycemic targets. We aimed to assess the efficacy of glucose-responsive insulin and glucagon closed-loop delivery for controlling glucose levels in adults with type 1 diabetes. METHODS: We conducted a randomized crossover trial involving 15 adults with type 1 diabetes, comparing standard insulin-pump therapy with dual-hormone, closed-loop delivery. Patients were admitted twice to a clinical research facility and received, in random order, both treatments. Each 15-hour visit (from 1600 to 0700) included an evening exercise session, followed by a medium-sized meal, a bedtime snack and an overnight stay. During visits that involved closed-loop delivery, basal insulin and glucagon miniboluses were delivered according to recommendations based on glucose sensor readings and a predictive dosing algorithm at 10-minute intervals. During visits involving standard insulin-pump therapy (control visits), patients used conventional treatment. RESULTS: Dual-hormone closed-loop delivery increased the percentage of time for which patients' plasma glucose levels were in the target range (median 70.7% [interquartile range (IQR) 46.1%-88.4%] for closed-loop delivery v. 57.3% [IQR 25.2%-71.8%] for control, p = 0.003) and decreased the percentage of time for which plasma glucose levels were in the low range (bottom of target range [< 4.0 mmol/L], 0.0% [IQR 0.0%-3.0%] for closed-loop delivery v. 10.2% [IQR 0.0%-13.0%] for control, p = 0.01; hypoglycemia threshold [< 3.3 mmol/L], 0.0% [IQR 0.0%-0.0%] for closed-loop delivery v. 2.8% [IQR 0.0%-5.9%] for control, p = 0.006). Eight participants (53%) had at least 1 hypoglycemic event (plasma glucose < 3.0 mmol/L) during standard treatment, compared with just 1 participant (7%) during closed-loop treatment (p = 0.02). INTERPRETATION: Dual-hormone, closed-loop delivery guided by advanced algorithms improved short-term glucose control and reduced the risk of hypoglycemia in a group of 15 adults with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01297946.
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In bihormonal closed-loop glucose control, glucagon has been used subcutaneously along with insulin for protection against hypoglycemia.
“More recently, in a bihormonal closed-loop glucose control, glucagon has been used subcutaneously along with insulin for protection against hypoglycemia.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [6]
In bihormonal closed-loop systems, small doses of glucagon are frequently administered.
“In this context, small doses of glucagon are frequently administered.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [6]
Haidar et al.'s randomized crossover trial showed improvement of glucose control against hypoglycemia with nocturnal glucagon plus insulin closed-loop strategy over open-loop insulin infusion.
“the most recent randomized crossover trial by Haidar et al.,6 which also showed improvement of glucose control against hypoglycemia with nocturnal glucagon plus insulin closed-loop strategy over open-loop insulin infusion.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [6]
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- Authors
- Haidar, A., Legault, L., Dallaire, M., Alkhateeb, A., Coriati, A., Messier, V., Cheng, P., Millette, M., Boulet, B., & Rabasa-Lhoret, R.
- Affiliations
- Montreal Children's Hospital (CA)
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Joule Inc.
- Published
- 2013-01-28
- Volume
- 185
- Issue
- 4
- Pages
- 297-305
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC3589308
- OpenAlex
- W2083628344
- Cited by
- 167
- References
- 22
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 14 · 2018: 17 · 2017: 14 · 2016: 16 · 2015: 22 · 2014: 28 · 2013: 13
- FWCI
- 20.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- other-oa
- Locations
- Canadian Medical Association Journal (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- AstraZeneca
- Sanofi
- Canadian Diabetes Association
- Diabète Québec
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
- Keywords
- type 1 diabetes, artificial pancreas, glucose-responsive insulin, glucagon, glycemic control, hypoglycemia, insulin pump therapy, glucose sensor, adults with type 1 diabetes, bedtime snack, hypoglycemia risk reduction
- MeSH terms
- Adult, Algorithms, Blood Glucose, Decision Support Techniques, Diabetes Mellitus, Type 1, Drug Administration Schedule, Drug Therapy, Combination, Female, Glucagon, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin Infusion Systems, Male, Regression Analysis, Biomarkers, Infusion Pumps, Implantable, Treatment Outcome, Cross-Over Studies, Pancreas, Artificial, Insulin Aspart
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