Milena Jancev¹, M.D., Frank J. Snoek², Ph.D., Miriam P. van der Meulen³, Ph.D., Heleen C. Knottnerus⁴, B.A., Lyan B. Vlaskamp⁵, M.Sc., Maureen F.T. Witkop⁵, M.Sc., Karel G.M. Moons³, Ph.D., Harold W. de Valk¹, M.D., Ph.D.,* Arianne C. van Bon⁶, M.D., Ph.D.*, J. Hans DeVries⁷, M.D., Ph.D.*, Erik H. Serné⁸, M.D., Ph.D.*, Thomas T. van Sloten¹, M.D., Ph.D.*, for the DARE Study Group.

* Contributed equally.

1. Department of Vascular Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands.
2. Department of Medical Psychology, Amsterdam University Medical Center, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
3. Department of Epidemiology & Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
4. Dutch Diabetes Association, Amersfoort, the Netherlands.
5. Inreda Diabetic, Goor, the Netherlands.
6. Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands.
7. Department of Endocrinology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
8. Departement of Internal Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

 

m.jancev-3@umcutrecht.nl

Background
Dual-hormone fully closed-loop systems deliver both insulin and glucagon and have the potential to improve glycemic control while reducing self-management burden in type 1 diabetes. The long-term efficacy and safety of dual-hormone fully closed-loop systems are unclear.

Methods
In this multicenter, open-label, randomized controlled trial, adults with type 1 diabetes were randomized (1:1) to a dual-hormone fully closed-loop (Inreda-AP) or usual care, either multiple daily insulin injections and continuous glucose monitoring (trial cohort A) or a hybrid closed-loop system (trial cohort B). Primary outcome was the percentage of time in the target range of 70-180 mg/dL (3.9-10.0 mmol/L) at 12 months. ClinicalTrials.gov-number: NCT05669547.

Results
243 participants aged 18-72 years (70 in trial-cohort A and 173 in trial-cohort B) underwent randomization. Over 12 months, in trial cohort A, the time in target range increased from 60.8±16.3% to 64.8±13.8% in the fully closed-loop group and remained stable in the usual-care group from 52.1±15.1% to 52.4±18.7% (adjusted mean difference=8.3% (95%CI:1.0-15.6, P=0.03)). In trial cohort B, the time in target range increased from 64.3±15.1% to 66.1±10.1% in the fully closed-loop group and remained stable (from 66.8±11.9% to 66.8±13.2%) in the usual-care group (adjusted mean difference=-0.4% (95%CI:-3.7-2.9, P=0.80). Nine severe hypoglycemic events occurred in the fully closed-loop group and two in the usual-care group.

Discussion/Conclusion
In this trial involving adults with type 1 diabetes, dual-hormone fully closed-loop therapy resulted in an increase in time in range compared to multiple daily insulin injections therapy, but not compared to hybrid closed-loop therapy.