Randomized trial in NEJM shows hybrid closed‑loop insulin pump improves A1c and reduces severe hypoglycemia in type 1 diabetes

A six-month randomized multicenter trial published Wednesday in the *New England Journal of Medicine* showed that a hybrid closed-loop insulin pump improved glycated hemoglobin (A1c) and reduced severe hypoglycemia in people with type 1 diabetes. According to the study funded by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases, the system increased the percentage of time glucose levels stayed within the target range compared with a sensor-augmented insulin pump.

The six-month trial, known as the International Diabetes Closed Loop (iDCL) Trial and registered as NCT03563313, randomly assigned adults and adolescents with type 1 diabetes in a 2-to-1 ratio to use either a hybrid closed-loop insulin delivery system or a sensor-augmented insulin pump, according to the study published Wednesday in the *New England Journal of Medicine* (NEJM). Funded by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the trial measured the primary endpoint as the percentage of time glucose levels remained within the target range of 70 to 180 mg/dL over six months, using continuous glucose monitoring.

The closed-loop system increased the average time in target glucose range from 61% ± 17% at baseline to 71% ± 12%, while the control group’s time in range remained essentially unchanged at 59% ± 14%, the study reported.

The adjusted mean difference between groups was 11 percentage points (95% confidence interval [CI], 9 to 14; P<0.001), equivalent to approximately 2.6 additional hours per day spent in the target range with closed-loop therapy. The closed-loop group also experienced 10 percentage points less time in hyperglycemia and 0.88 percentage points less time in hypoglycemia (below 70 mg/dL), translating to roughly 2.4 fewer hours per day in high glucose levels and 13 fewer minutes per day in low glucose levels compared with the control group.

The trial demonstrated improved glycated hemoglobin (A1c) levels in the closed-loop group compared with the sensor-augmented pump group, according to the authors. This improvement in A1c coincided with the increased time in range and reductions in both hyperglycemia and hypoglycemia over the study period. The authors concluded that the closed-loop system led to a greater percentage of time with glucose levels in the target range, less hyperglycemia and hypoglycemia, and better A1c levels than the sensor-augmented pump.

Safety outcomes showed low and comparable rates of severe hypoglycemia and diabetic ketoacidosis (DKA) between the two groups. The authors noted no excess of serious adverse events with closed-loop therapy, underscoring a favorable risk-benefit profile. Records from the trial indicated that severe hypoglycemia and DKA events were rare across both arms during the six-month period.

Additional NEJM trials in younger populations have reported similar findings. A trial involving children aged 2 to under 6 years (PEDAP; NCT04796779) found that hybrid closed-loop therapy increased time in target glucose range by 12.4 percentage points (95% CI, 9.5 to 15.3; P<0.001), or about three hours per day, compared with standard care using continuous glucose monitoring and usual insulin delivery. The mean difference in A1c between closed-loop and standard care was −0.42 percentage points (95% CI, −0.62 to −0.22; P<0.001), favoring the closed-loop group. Importantly, this improvement occurred without a significant increase in time spent below 70 mg/dL, indicating enhanced glycemic control without increased hypoglycemia risk. Severe hypoglycemia events were infrequent, with two cases in the closed-loop group and one in the standard-care group over the 13-week study.

Another NEJM trial evaluating a Cambridge hybrid closed-loop algorithm in very young children reported improved glycemic control compared with sensor-augmented pump therapy over 16 weeks, with no increase in hypoglycemia or serious adverse events. That trial recorded one severe hypoglycemic event during the closed-loop period and no episodes of DKA.

Broader NEJM research has also examined closed-loop insulin delivery in pregnancy complicated by type 1 diabetes and in children and adolescents with new-onset disease. In pregnancy, hybrid closed-loop therapy significantly improved maternal glycemic control compared with standard care without unanticipated safety concerns, according to published findings. A separate trial assessing closed-loop therapy’s impact on C-peptide secretion in new-onset type 1 diabetes found that while glycemic targets were better managed, the decline in beta-cell function was not slowed over 24 months.

Collectively, these NEJM trials, supported by federal funding and conducted across multiple centers, provide evidence that hybrid and closed-loop insulin delivery systems improve time in glucose target range and lower A1c in diverse patient populations with type 1 diabetes. The studies consistently report low rates of severe hypoglycemia and DKA and no increase in serious adverse events under trial conditions. These findings contribute to the growing body of data supporting automated insulin delivery as a safe and effective approach to glycemic management in type 1 diabetes.