Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial

Abstract

In adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol^-1 (9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9-10.0 mmol l^-1). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0-42.6 percentage points; P < 0.001). Time > 10.0 mmol l^-1 was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, -35.2 percentage points; 95% CI, -42.8 to -27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l^-1 versus 12.6 ± 3.0 mmol l^-1, respectively; mean difference, -3.6 mmol l^-1; 95% CI, -4.6 to -2.5 mmol l^-1; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol^-1 (7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol^-1 (8.7% ± 1.2%); mean difference, -15 mmol mol^-1; 95% CI, -11 to -20 mmol l^-1 (mean difference, -1.4%; 95% CI, -1.0 to -1.8%); P < 0.001). Time < 3.9 mmol l^-1 was similar between treatments (a median of 0.44% (interquartile range, 0.19-0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00-1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).

Fig. 1. Participant flow.

Overview of the participant flow.

Fig. 2. Glucose control during closed-loop and control periods.

a, Median sensor glucose measurements during closed-loop insulin delivery and control insulin therapy (the patients' usual therapy). Red and gray shaded areas, IQR for each treatment. The values are reported during a 24-h period from midnight to midnight. Black horizontal dashed lines, lower and upper limits of the glucose target range of 3.9–10.0 mmol l⁻¹. b, Median amount of algorithm-directed insulin delivery during the closed-loop intervention. Shaded area, IQR.

Extended Data Fig. 1. Individual participants’ time spent in target range 3.9–10.0 mmol/L (n = 26).

Overall mean is shown in red.