Pierre-Yves Benhamou1, Sylvia Franc2, Yves Reznik3, Charles Thivolet4, Pauline Schaepelynck5, Eric Renard6, Bruno Guerci7, Lucy Chaillous8, Celine Lukas-Croisier9, Nathalie Jeandidier10, Helene Hanaire11, Sophie Borot12, Maeva Doron13, Pierre Jallon13, Ilham Xhaard14, Vincent Melki11, Laurent Meyer10, Brigitte Delemer9, Marie Guillouche8, Laurene Schoumacker-Ley7, Anne Farret6, Denis Raccah5, Sandrine Lablanche15, Michael Joubert3, Alfred Penfornis16, Guillaume Charpentier14. 1. Department of Endocrinology, Grenoble University Hospital, INSERM U1055, Grenoble Alpes University, Grenoble, France. Electronic address: pybenhamou@chu-grenoble.fr. 2. Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes, France; Center for Study and Research for Improvement of the Treatment of Diabetes, Bioparc-Genopole Evry-Corbeil, Evry, France. 3. Department of Endocrinology, University of Caen Côte de Nacre Regional Hospital Center, Caen, France. 4. Department of Endocrinology, Diabetology, Nutrition, Hospices Civils de Lyon, Lyon, France. 5. Department of Diabetology, Marseille University Hospital, Marseille, France. 6. Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, UMR CNRS 5203, INSERM U1191, University of Montpellier, Montpellier, France. 7. Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition, Lorraine University Hospital, Vandoeuvre Lès Nancy, France. 8. Department of Endocrinology, Diabetology, Nutrition, L'Institut du Thorax, Centre Hospitalier Universitaire de Nantes, Nantes, France. 9. Department of Endocrinology, Diabetology, Reims University Hospital, Reims, France. 10. Department of Endocrinology, Diabetology and Nutrition, Strasbourg University Hospital, Strasbourg, France. 11. Department of Diabetology, Metabolic Diseases and Nutrition, Toulouse University Hospital, Toulouse, France. 12. Department of Endocrinology, Nutrition and Diabetes, Besançon University Hospital and Franche-Comté University, Besançon, France. 13. Laboratoire d'électronique des technologies de l'information, F-38000, Grenoble Alpes University, Grenoble, France. 14. Center for Study and Research for Improvement of the Treatment of Diabetes, Bioparc-Genopole Evry-Corbeil, Evry, France. 15. Department of Endocrinology, Grenoble University Hospital, INSERM U1055, Grenoble Alpes University, Grenoble, France. 16. Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes, France; Paris Sud University, Paris, France.
Abstract
BACKGROUND:Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. METHODS: In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. FINDINGS:Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. INTERPRETATION: The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. FUNDING: French Innovation Fund, Diabeloop.
RCT Entities:
BACKGROUND: Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. METHODS: In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. FINDINGS: Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. INTERPRETATION: The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. FUNDING: French Innovation Fund, Diabeloop.
Authors: Roy W Beck; Steven J Russell; Edward R Damiano; Firas H El-Khatib; Katrina J Ruedy; Courtney Balliro; Zoey Li; Peter Calhoun Journal: Diabetes Technol Ther Date: 2022-10 Impact factor: 7.337