NEJM publishes impressive Cambridge study testing closed-loop in pregnancy for up to 3+ months, including during labor – August 19, 2016

NEJM published remarkable data yesterday from the Cambridge closed-loop team: “Closed-Loop Insulin Delivery during Pregnancy in Women with Type 1 Diabetes.” In the randomized, crossover study, 16 pregnant women with type 1 diabetes completed four weeks of overnight closed-loop vs. four weeks of sensor-augmented pump (SAP) therapy. Fourteen of the women choose to continue using the hybrid closed loop system 24/7 up to an additional 14.6 weeks, including during labor, delivery, and in the first 48 hours after delivery – wow!

The results were excellent during both phases. Overnight time in a very tight target (63-140 mg/dl) was 75% during the four weeks of overnight closed-loop vs. 60% during the four weeks of SAP (p=0.002), with a lower average glucose (119 vs. 133 mg/dl) and no significant difference in hypoglycemia (1.3% vs. 1.9%) or insulin dose. Figure 1 from the paper (see below) really puts the improvement into perspective. During the continuation phase (an impressive median of 11.6 weeks), glucose levels were in the target range 69% of the time with 24/7 closed-loop, including a mean blood glucose of 126 mg/dl. Closed-loop was very effective immediately before and after delivery: time-in-range was 87% in the 24 hours before delivery (median glucose: 110 mg/dl) and 74% in the first 48 hours after delivery (median glucose: 117 mg/dl) – the pre-post delivery data for each subject (see below) highlights the strong control.

The study is a big win for the field for a number of reasons: (i) strong results in a highly challenging population in which to test closed-loop (highly variable insulin doses); (ii) strong efficacy over the SAP control arm, where motivation is very high (pregnant women); (iii) a long outpatient study duration (more than three months of closed-loop use); (iv) a technology-naïve study population (14 of 16 participants had no CGM experience before the study); and (v) the fourth NEJM closed-loop paper in the past three years, including the second in the past 11 months for the Cambridge team (Cambridge in September 2015; BU/MGH in June 2014; DREAM in February 2013). We’re especially glad to see studies moving into special populations, where closed loop may show even bigger benefits than typical study participants.

• The study used an Abbott FreeStyle Navigator II CGM, a Dana R Diabecare pump (Bluetooth), and an MPC control algorithm running on a Dell tablet. Insulin decisions were made every 12 minutes, and the algorithm targeted 97-124 mg/dl. During the four-week crossover phase, participants were instructed to start closed-loop insulin delivery after their evening meal and to stop it before breakfast the next morning. Pre-meal boluses were given manually (15-30 minutes before eating), using the bolus calculator on the insulin pump.
• We’re still not sure if the Cambridge team plans to commercialize its algorithm, though its upcoming studies will use Medtronic’s MiniMed 640G/Enlite 3 and an Android phone running Cambridge’s MPC algorithm.

Figure 1: Median Sensor-Recorded Glucose Values over a 24-Hour Period with Sensor-Augmented Pump Therapy and Closed-Loop Insulin Delivery

Figure 2: Glycemic Control during Labor and Delivery in the 14 Participants Who Continued to Use Closed-Loop Insulin Delivery

-- by Adam Brown and Kelly Close