Dual-hormone fully closed-loop therapy versus multiple daily insulin injections or hybrid closed-loop therapy in adults with type 1 diabetes: a multicentre, open-label, randomised controlled trial

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. This study aimed to investigate the long-term efficacy and safety of the dual-hormone fully closed-loop in adults with type 1 diabetes. 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. Findings A total of 243 participants (mean ± SD age 48.7 ± 14 years, 44% female), with 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 (mean ± SD) 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 to 2.9, P=0.80). In total, 59/119 (50%) participants discontinued the intervention during the trial. In the fully closed-loop group 9 severe hypoglycemic events occurred, and 2 in the usual-care group. Interpretation 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. Also, there were more hypoglycemic events in the dual-hormone fully closed-loop therapy group and a relatively high number of participants discontinued the dual-hormone fully closed-loop during the trial. Funding This study was funded by the Dutch National Healthcare Institute and ZonMw.