A cohort of patients with type 1 diabetes, including children as young as age 6 years, treated with insulin pump therapy experienced a 10% improvement in time spent in the recommended glycemic range when randomly assigned to 12 weeks using a hybrid closed-loop insulin delivery system, according to findings published in The Lancet and presented at the European Association for the Study of Diabetes annual meeting.
The open-label study, conducted across centers in the U.K. and the U.S., was one of the first artificial pancreas trials to include both children and patients with an HbA1c of at least 7.5%, demonstrating that the technology is potentially beneficial for a wide range of people with diabetes.
“According to two recent meta-analyses, home use of a single-hormone closed-loop system is an efficacious and safe therapeutic approach for people with type 1 diabetes; however, most of the [randomized controlled trials] included in these analyses have some limitations: small samples sizes, short intervention periods, and mainly conducted in adults,” Martin Tauschmann, MD, of the Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, U.K., said during a presentation. “Only two studies were long enough to report HbA1c outcomes, so there is a need for longer, larger trials in order to allow a wider adaptation and to support reimbursement of hybrid closed-loop insulin delivery systems.”
Tauschmann and colleagues analyzed data from 86 patients with type 1 diabetes aged at least 6 years using sensor-augmented insulin pump therapy, with an HbA1c of at least 7.5%, recruited from diabetes outpatient clinics at four hospitals in the U.K. and two centers in the U.S. (33 patients aged 6-12 years). Researchers randomly assigned patients to hybrid closed-loop therapy (n = 46; mean age, 22 years; 48% female) or to remain on sensor-augmented pump therapy (n = 40; mean age, 21 years; 55% male) for 12 weeks in free-living conditions. Primary endpoint was the between-group difference in the proportion of time spent in the target glucose range (70-180 mg/dL), based on sensor-measured glucose concentrations.
At 12 weeks, researchers found that the proportion of time spent in the target glucose range was 10.8 percentage points higher in the closed-loop group vs. the pump-therapy control group (65% vs. 54%), with results observed across all age groups with both high and low baseline HbA1c values.
“A consistent difference of 10-15 percentage points occurred between the two groups across the whole range of time-in-range values, and a difference of nearly 20 percentage points among users with the highest time in range in the two groups,” the researchers wrote.
Hybrid closed-loop therapy also reduced mean glucose (P < .0001) and time spent above the target glucose range (P < .0001) vs. the control group, according to researchers, whereas glucose variability was also lower among patients assigned to the closed-loop group (P < .0001).
There were no between-group differences for total daily insulin dose or body weight change during the trial, according to researchers. There were no incidents of severe hypoglycemia. One case of diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure.
“Our closed-loop control algorithm works well across all ages in sub-optimally controlled type 1 diabetes, improving glucose control and reducing the risk for hypoglycemia,” Roman Hovorka, PhD, FMedSci, professor at the Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, U.K, told Endocrine Today. “Closed-loop should be embraced by the clinical practitioners and considered for reimbursement.”
In commentary published in The Lancet accompanying the findings, Alfonso Galderisi, MD, of the department of women’s and children’s health at the University of Padova, Italy, and Jennifer L. Sherr, MD, PhD, of the department of pediatric endocrinology at Yale University School of Medicine, wrote that evidence on the use of closed-loop systems in preadolescents “falls short,” as does the inclusion of patients with an HbA1c of at least 7.5%.
“Therefore, it is inherently difficult to generalize the results from many hybrid closed-loop trials to the more heterogeneous population living with type 1 diabetes,” Galderisi and Sherr wrote. “Furthermore, insurance coverage of these devices might be impeded if patients requesting such systems do not mimic the characteristics of the participants in a trial.”
In a press release announcing the findings, Daniel Finan, PhD, research director at JDRF, which supported the study, said the results further demonstrate that artificial pancreas technology improves outcomes and reduces disease burden for people with diabetes.
“In particular, this study demonstrates that people with diabetes who have suboptimal control can benefit greatly from such technology,” Finan said in the release. – by Regina Schaffer
Tauschmann M. Oral presentation #90. Presented at: European Association for the Study of Diabetes Annual Meeting; Oct. 1-5, 2018; Berlin.
Tauschmann M, et al. Lancet. 2018;doi:10.1016/s0140-6736(18)31947-0.
For more information:
Roman Hovorka, PhD, FMedSci, can be reached at the University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Box 289, Addenbrooke’s Hospital, Hills Rd, Cambridge CB2 0QQ, UK; email: firstname.lastname@example.org.
Disclosures: The JDRF, National Institute of Health Research and the Wellcome Trust supported this study. Hovorka reports he has received speaking fees from Eli Lilly and Novo Nordisk, served on an advisory panel for Eli Lilly and has received licensing fees from BBraun and Medtronic. Tauschmann reports he has received speaking fees from Medtronic and Novo Nordisk. Please see the study for the other authors’ relevant financial disclosures.