Closed-Loop Insulin Delivery Versus Sensor-Augmented Pump Therapy in Older Adults With Type 1 Diabetes (ORACL): A Randomized, Crossover Trial

• Published in: Diabetes care Vol. 45; no. 2; pp. 381 - 390
• Main Authors: McAuley, Sybil A, Trawley, Steven, Vogrin, Sara, Ward, Glenn M, Fourlanos, Spiros, Grills, Charlotte A, Lee, Melissa H, Alipoor, Andisheh Mohammad, O'Neal, David N, O'Regan, Niamh A, Sundararajan, Vijaya, Colman, Peter G, MacIsaac, Richard J
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-02-2022
• Subjects: Adults; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Closed loops; Cross-Over Studies; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - drug therapy; Diabetic ketoacidosis; Glucose monitoring; Humans; Hypoglycemia; Hypoglycemic Agents - therapeutic use; Insulin; Insulin Infusion Systems; Ketoacidosis; Middle Aged; Older people; Research design; Safety; Sensors; Therapy
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc21-1667

To assess the efficacy and safety of closed-loop insulin delivery compared with sensor-augmented pump therapy among older adults with type 1 diabetes.
This open-label, randomized (1:1), crossover trial compared 4 months of closed-loop versus sensor-augmented pump therapy. Eligible adults were aged ≥60 years, with type 1 diabetes (duration ≥10 years), using an insulin pump. The primary outcome was continuous glucose monitoring (CGM) time in range (TIR; 3.9-10.0 mmol/L).
There were 30 participants (mean age 67 [SD 5] years), with median type 1 diabetes duration of 38 years (interquartile range [IQR] 20-47), randomized (n = 15 to each sequence); all completed the trial. The mean TIR was 75.2% (SD 6.3) during the closed-loop stage and 69.0% (9.1) during the sensor-augmented pump stage (difference of 6.2 percentage points [95% CI 4.4 to 8.0]; P < 0.0001). All prespecified CGM metrics favored closed loop over the sensor-augmented pump; benefits were greatest overnight. Closed loop reduced CGM time <3.9 mmol/L during 24 h/day by 0.5 percentage points (95% CI 0.3 to 1.1; P = 0.0005) and overnight by 0.8 percentage points (0.4 to 1.1; P < 0.0001) compared with sensor-augmented pump. There was no significant difference in HbA1c between closed-loop versus sensor-augmented pump stages (7.3% [IQR, 7.1-7.5] (56 mmol/mol [54-59]) vs. 7.5% [7.1-7.9] (59 mmol/mol [54-62]), respectively; P = 0.13). Three severe hypoglycemia events occurred during the closed-loop stage and two occurred during the sensor-augmented pump stage; no hypoglycemic events required hospitalization. One episode of diabetic ketoacidosis occurred during the sensor-augmented pump stage; no serious adverse events occurred during the closed-loop stage.
Closed-loop therapy is an effective treatment option for older adults with long-duration type 1 diabetes, and no safety issues were identified. These older adults had higher TIR accompanied by less time below range during closed loop than during sensor-augmented pump therapy. Of particular clinical importance, closed loop reduced the time spent in hypoglycemic range overnight.