A Comparison of Two Hybrid Closed-Loop Systems in Adolescents and Young Adults with Type 1 Diabetes: A Multicenter Randomized Crossover Trial

Abstract

Background: Management of type 1 diabetes (T1D) is challenging. We compared outcomes using a commercially-available hybrid closed loop system versus a new investigational system with features potentially useful for adolescents and young adults with T1D. Methods: In this open-label, multi-national, seven center, randomized crossover trial, participants 14 to 29 years old, with type 1 diabetes and HbA1c 7·0% to 11·0% (53 mmol/mol to 97 mmol/mol), at seven diabetes centers used a Medtronic MiniMed™ 670G hybrid closed-loop system (670G) during one 12-week period and a Medtronic advanced hybrid closed-loop system (AHCL) during the other period. In an intention-to-treat analysis, co-primary outcomes, measured with continuous glucose monitoring, were percent time >180 mg/dL (>10·0 mmol/L) from 6AM to 11:59PM tested for superiority and time <54 mg/dL (<3·0 mmol/L) calculated over the full 24-hours tested for noninferiority (non-inferiority margin 2%). Findings: From June 3, 2019 to August 22, 2019, 113 individuals entered the trial. Mean percentage of time with daytime glucose levels >180 mg/dL (>10·0 mmol/L) was 42% ± 13% at baseline, 37% ± 9% during the 670G arm, and 34% ± 9% during the AHCL arm (mean difference [AHCL minus 670G] = -3%; 95% CI -4% to -2%, P<0·001). Mean 24-hour percentage of time with glucose levels <54 mg/dL (<3∙0 mmol/L) was 0·46% ± 0·42% at baseline, 0·50% ± 0·35% during the 670G arm and 0∙46% ± 0∙33% in the AHCL arm (mean difference [AHCL minus 670G] = -0·06%; 95% CI -0·11% to -0·02%; P<0·001 for non-inferiority). One severe hypoglycemia event occurred in the AHCL arm and none in the 670G arm. Interpretation: Hyperglycemia was reduced without increasing hypoglycemia in adolescents and young adults with type 1 diabetes using the investigational AHCL system compared with the commercially-available MiniMed 670G system. Trial Registration: The trial is registered with Clinicaltrials.gov: NCT03040414. Funding: National Institutes of Health UC4DK108611 Declaration of Interests: Financial funding support: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (IUC4DK10861); grant provided to Jaeb Center for Health Research and paid to each of the investigator’s institutions. Non-financial support: Medtronic Inc; provided study CGM devices and sensors. Additional financial disclosures are as follows: R. Bergenstal, R. Beck, A. Criego, D. Schatz, S. Weinzimer, J. Sibayan, M. Johnson, R. Bailey, P. Calhoun, A. Carlson, E. Isganaitis, R. Bello, A. Albanese-O’Neill, K. Weyman; and K. Hood report no conflicts of interest. R. Nimri reports ownership in DreaMed. L. Laffel reports consulting with Medtronic, Sanofi, NovoNordisk, Boehringer Ingelheim, and Dexcom. T. Battelino reports consulting for Medtronic, NovoNordisk, and Eli Lilly and ownership in DreaMed. T. Danne reports consulting for DreaMed. K. Dovc reports consulting for Sanofi. T. Biester reports speaking engagements for Medtronic and Roche. M. Phillip reports ownership in DreaMed and consulting for NovoNordisk, Sanofi, and Pfizer. Ethics Approval Statement: The protocol and informed consent/assent forms were approved by the appropriate institutional review boards and ethics committees, and regulatory approval to conduct the study was obtained in all four countries.