The Medtronic MiniMed™ 670G hybrid closed-loop system was approved for use in type 1 diabetes by the FDA in 2016 for adults and adolescents ages ≥14 and in 2018 for children ages 7-13 based on safety and its efficacy of reducing glycated hemoglobin (A1C) in the pivotal trials. The standard metrics used in these trials showed that A1C was reduced by 7% relative decrease (from 7.4% to 6.9%; p‹0.001) and time in hypoglycemia ‹70 mg/dL was reduced by 44% in 124 adults/adolescents. In 105 children A1C was reduced by 5% relative decrease (from 7.9% to 7.5%; p‹0.001) and time in hypoglycemia (‹70 mg/dL) by 36% (from 4.7% to 3.0%; p‹0.001). Because these standard metrics may underestimate the effectiveness of the MiniMed™ 670G system, we used novel composite metrics derived from continuous glucose monitoring (CGM) to better understand how the 670G may improve glycemic control beyond A1C.
CGM-derived data from the 2-week run-in and 3-month study phases of the adult/adolescent and pediatric MiniMed™ 670G pivotal trials were analyzed. The areas-under-the-curve (AUC), frequency, and duration of hypoglycemia ‹70 mg/dL (the “hypo-triad”) were used to derive the “intensity” and “volume” of hypoglycemia (1). The Comprehensive Glucose Pentagon (CGP) area was calculated using the mean glucose, intensity of hypoglycemia and hyperglycemia, time-out-of-range (TOR=reciprocal of time-in-range) and coefficient of variation (2).
(1) Vigersky RA et al. J Diab Sci Tech. 2018; 12(1): 114-123.
(2) Thomas A et al. J Diab Sci Tech. 2018; 12(1):69-75.
The “hypo-triad” analysis showed that there was a reduction in intensity (-43%) and volume (-71%) of hypoglycemia between the run-in and study phases in adults/adolescents. In pediatric subjects, there was a 37% reduction in intensity and 61% reduction in volume of hypoglycemia 70 mg/dL. The CGP area was reduced by 8% from the run-in phase compared with the study phase, in adults and adolescents. The CGP area was reduced by 12% in the pediatric trial.
We are looking “beyond A1C” because it provides no information about hypoglycemia, hyperglycemia or glycemic variability, its relationship to mean glucose is individualized, and its accuracy is affected by a variety of clinical conditions, e.g., hemoglobinopathies, anemia, uremia and pregnancy.
Conclusion : The results of the Medtronic MiniMedTM 670G system pivotal trials with novel “hypo-triad” and CGP demonstrate a more robust and clinically relevant improvement in overall glycemic control using this technology compared with using standard metrics such as A1C.
Robert Vigersky– Principal Medical Officer, Medtronic Diabetes
Andreas Thomas– Scientific Manager Germany, Medtronic Diabetes
John Shin– Sr. Director of Clinical Research, Biostatistics, and Bioinformatics, Medtronic Diabetes
Boyi Jiang– Sr Advanced Analytics Analyst, Medtronic Diabetes
Chantal McMahon– Lead for Data & Digital Innovations, Medtronic Diabetes
Principal Medical Officer
Robert A. Vigersky, M.D. is Senior Medical Director of Medtronic Diabetes and Professor of Medicine at the Uniformed Services University of the Health Sciences. He graduated as the Valedictorian from Boston University School of Medicine, did his Internal Medicine training at The Johns Hopkins Hospital, and completed a 3-year Fellowship in Endocrinology at the NIH. He has had a distinguished career that has included Academia (at Walter Reed where he established the Diabetes Institute), Private Practice (where he was President of the Endocrine and Diabetes Group of Washington and Director of the Diabetes Treatment Center at Georgetown University Hospital and the Washington Hospital Center), and Industry (at Medtronic). He has been an active participant in the Endocrine Society where established Clinical Practice Guideline program and served as President from 2009-2010 and the Diabetes Technology Society which gave him its Leadership Award in 2011. Dr. Vigersky has published over 280 scholarly papers and abstracts focusing on the use of technology to improve outcomes of patients with diabetes.
Scientific Manager Germany
Dr. Andreas Thomas is the Senior Scientific Manager for Medtronic Diabetes in Germany. He is also a Senior Scientific Assistant in Physics at the Technical University, Dresden, Germany. He has over 340 scientific publications in English and German.
Sr. Director of Clinical Research, Biostatistics, and Bioinformatics
Dr. John Shin is Sr. Director of Clinical Research, Biostatistics, and Bioinformatics at Medtronic Diabetes where he has been employed for over 20 years. He holds BS, MS, and Ph.D. degrees in Biomedical Engineering from the University of Southern California. .
Sr Advanced Analytics Analyst
Dr. Boyi Jiang Boyi received his PhD from the Department of Systems & Information Engineering at the University of Virginia. His research
for the Center for Diabetes Technology focused on physiological modeling, control design and application development of closed loop
insulin delivery system. At Medtronic Diabetes he currently is a member of the advanced sensor analytics team.
Lead for Data & Digital Innovations
Dr. Chantal McMahon is the Data & Digital Innovations Lead for Medtronic Diabetes. She has a BS in Biomedical Engineering from the University of Rochester and a Ph.D. in Biomedical Engineering from Drexel University. She has over 10 years of experience in biotechnology, healthcare, medical devices, research design and execution.