Pivotal trial: Time-in-range improved, 96% say system easy to use
The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.
The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.
After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.
Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.
There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.
Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.
The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.
In a study questionnaire, 96% reported that the system was easy to use.
AHCL vs 670G: Major improvements seen
Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.
“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.
FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.
The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.
The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.
“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.
Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.
“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.
One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.
The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.
“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.