Artificial pancreas treatment, also referred to as closed loop glucose control, is an emerging treatment option combining an insulin pump and continuous glucose monitoring with a control algorithm to deliver insulin in a glucose responsive manner (that is, a single hormone artificial pancreas system). Glucagon can also be delivered in a similar glucose responsive fashion, as accommodated by dual hormone artificial pancreas systems. Therefore, compared with insulin pumps or sensor augmented pumps, artificial pancreas use can reduce the burden for patients by automatically adjusting the amount of insulin entering the body on the basis of sensor glucose levels. Several artificial pancreas systems have been developed, and their safety and efficacy have been evaluated in many studies, showing promising results.
Objective To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes.
Design Systematic review and meta-analysis of randomized controlled trials.
Data sources Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018.
Eligibility criteria for selecting studies Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality.
Results 40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual-hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favorable effect on the proportion of time with sensor glucose level above 10 mmol/L (−8.52%, −11.14% to −5.9%) or below 3.9 mmol/L (−1.49%, −1.86% to −1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems.
Conclusions Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.
Closed loop systems have four components: the pump, a continuous glucose monitoring system, the decision making microprocessor, and a system that adjusts infusion rate. The microprocessor replaces human decision making, and makes more frequent dose adjustments than a person could. Closed loop systems may reduce the stress involved in self-managing diabetes.
Bekiari and colleagues systematically reviewed randomized trials of these systems, and concluded that people using them spent about 10% more time near normoglycaemia than controls using other insulin treatments. However, the overall evidence base is weak. Many trials in the review were of low quality. Type 1 diabetes is lifelong, but most trials are short—of 41 trials included, 30 lasted seven days or less. In 16 trials, the closed loop system controlled blood glucose only overnight. Of 25 trials that evaluated closed loop systems over 24 hours, only one8 was long enough to measure glycated haemoglobin (HbA1c), which fell by only a clinically insignificant 0.3% (3.3 mmol/mol) after 12 weeks.
What does this new review mean for people with type 1 diabetes, and policy makers? Closed loop systems can improve control overnight, and reduce the burden of self-management during the day by reducing frequent decisions on adjustments to insulin dose. However, we do not know whether these systems reduce the long term complications of diabetes. For policy makers, there are insufficient data for cost effectiveness analysis.
We need longer and larger trials, in both adults and children, to compare closed loop systems with self-management using continuous glucose monitoring