Investigational artificial-pancreas systems uniformly appeared to improve glycemic control in outpatients in a new systematic review and meta-analysis, despite the different technologies tested and varying clinical conditions in the included clinical trials.
The analysis, which included 24 randomized controlled outpatient trials in a total of 585 patients, was published May 19 in Lancet  Diabetes & Endocrinology by Alanna Weisman, MD, of Mount Sinai Hospital, University of Toronto, Ontario, and colleagues.
The "artificial pancreas," also known as a "closed-loop" system, consists of an insulin infusion pump, a continuous glucose monitor, and software with dosing algorithms that link the two devices to automate insulin delivery.
The studies included both adult and pediatric patients with type 1 diabetes and both single-hormone (insulin) and dual-hormone (insulin plus glucagon) systems. Comparators were either sensor-augmented insulin pumps (used in 21 of the 22 single-hormone system trials) or pumps with blinded continuous glucose sensors (six of seven dual-hormone system studies).
While some of the results differed by the type of algorithm and whether or not remote monitoring was used, the primary outcome — time in target blood glucose range — was improved over currently available comparators in all trials.
"The bottom line is they all work," Dr Weisman told Medscape Medical News. "We're expecting some of these devices to hit the market in the next 1 to 2 years, and that will be a very exciting development. I think there will be a lot of questions about access once these are on the market."
In an accompanying editorial, Steven J Russell, MD, of the Diabetes Research Center at Massachusetts General Hospital, Boston, said, "These results support the growing conviction of those closely following this field that artificial-pancreas technologies will soon change the standard of care for patients with type 1 diabetes."
Dr Russell, a researcher on the dual-hormone device now known as the "ILet," also commented that upcoming data from larger trials for individual artificial-pancreas systems may obviate the need for future meta-analyses. But for now, "it is a measure of the progress in this field that sufficient data for meta-analysis have been generated and that the analysis shows that single-hormone and dual-hormone artificial-pancreas systems are both capable of increasing time in range and reducing hypoglycemia without increasing the use of insulin."
Artificial-Pancreas Systems Outperform Comparators
Overall, the artificial-pancreas systems produced a 12.59% increase in time spent in glycemic target range (P < .0001), corresponding to 172 minutes per day. This effect was greater for the dual- than for the single-hormone systems (19.52% vs 11.06%, 281 vs 159 minutes per day, both P < .0001 vs comparator).
Among 21 comparisons with 463 patients pooled to compared time in hypoglycemia (< 3.9 mmol/L, or < 70 mg/dL), that value was 2.45% lower with the artificial-pancreas systems (P < .0001), or 35 minutes per day, corresponding to a 50% risk reduction. This, too, was better with the dual-hormone systems (3.78% vs 1.88% for single-hormone systems, or 54 vs 27 minutes per day).
Differences in hypoglycemia reduction were greater among studies that included remote monitoring of the artificial-pancreas systems (-3.92% vs -0.63%, P = .01). However, in a post hoc analysis of studies where monitoring was performed in both arms, there was still a reduction in hypoglycemia with the artificial-pancreas systems, suggesting that the reduction in hypoglycemia wasn't merely due to the remote monitoring, Dr Weisman explained.
Among 18 comparisons with 389 patients, no differences were seen in insulin dose between those on artificial-pancreas systems and comparators (0.07 units per hour overall, P = .08), although insulin doses were significantly higher with the artificial-pancreas systems in children (P < .0001 vs 0.86 for adults).
Study Caveats and Future Endeavors
Dr Russell noted that the heterogeneity in the types of systems used as comparators in the single- vs dual-hormone studies — a study caveat raised by the authors — probably wouldn't have made a large difference in the results, since the times in range for those comparators didn't differ dramatically.
And, he noted that any remaining concerns about the remote-monitoring issue could be resolved with the results of a currently ongoing study that is directly assessing the effect of monitoring on hypoglycemia with the use of single- and dual-hormone artificial-pancreas systems.
According to Dr Weisman, the device 670G — the only one on the market thus far that automatically reduces high as well as low blood sugars — is actually a "hybrid" closed loop and therefore less automated than the more advanced systems used in the majority of studies in this analysis. "It's a stepping-stone, but not quite there yet."
Another possible caveat is that the patients enrolled in these trials had all previously used pumps with or without continuous glucose sensors and therefore typically had better control at baseline than the overall real-world type 1 diabetes population.
However, both Dr Weisman and Dr Russell noted that artificial-pancreas systems might improve glycemic control to an even greater extent for those currently taking injections and who may not be as technologically savvy, "depending on how easy they are to use and how much they demand of the user," Dr Russell said.
Indeed, Dr Weisman noted, "The whole purpose of these systems is to remove the patients from making the decisions. These systems are really effective in improving the time spent in target range, so if they have even more time out of range at baseline, there's even more room for improvement."
Lancet Diabetes Endocrinol. Published May 19, 2017. Abstract, Editorial
Lancet Diabetes Endocrinol. Published May 19, 2017.
Effect of artificial pancreas systems on glycaemic control in patients with type 1 diabetes: a systematic review and meta-analysis of outpatient randomised controlled trials
Dr Alanna Weisman, MD
Johnny-Wei Bai, BHSc
Marina Cardinez, MD
Caroline K Kramer, MD
Bruce A Perkins, MD
Published: 19 May 2017
Closed-loop artificial pancreas systems have been in development for several years, including assessment in numerous varied outpatient clinical trials. We aimed to summarise the efficacy and safety of artificial pancreas systems in outpatient settings and explore the clinical and technical factors that can affect their performance.
We did a systematic review and meta-analysis of randomised controlled trials comparing artificial pancreas systems (insulin only or insulin plus glucagon) with conventional pump therapy (continuous subcutaneous insulin infusion [CSII] with blinded continuous glucose monitoring [CGM] or unblinded sensor-augmented pump [SAP] therapy) in adults and children with type 1 diabetes. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from 1946, to Jan 1, 2017.
We excluded studies not published in English, those involving pregnant women or participants who were in hospital, and those testing adjunct medications other than glucagon. The primary outcome was the mean difference in percentage of time blood glucose concentration remained in target range (3·9–10 mmol/L or 3·9–8 mmol/L, depending on the study), assessed by random-effects meta-analysis. This study is registered with PROSPERO, number 2015:CRD42015026854.
We identified 984 reports; after exclusions, 27 comparisons from 24 studies (23 crossover and one parallel design) including a total of 585 participants (219 in adult studies, 265 in paediatric studies, and 101 in combined studies) were eligible for analysis. Five comparisons assessed dual-hormone (insulin and glucagon), two comparisons assessed both dual-hormone and single-hormone (insulin only), and 20 comparisons assessed single-hormone artificial pancreas systems. Time in target was 12·59% higher with artificial pancreas systems (95% CI 9·02–16·16; p<0·0001), from a weighted mean of 58·21% for conventional pump therapy (I2=84%). Dual-hormone artificial pancreas systems were associated with a greater improvement in time in target range compared with single-hormone systems (19·52% [95% CI 15·12–23·91] vs 11·06% [6·94 to 15·18]; p=0·006), although six of seven comparisons compared dual-hormone systems to CSII with blinded CGM, whereas 21 of 22 single-hormone comparisons had SAP as the comparator. Single-hormone studies had higher heterogeneity than dual-hormone studies (I2 79% vs 66%). Bias assessment characteristics were incompletely reported in 12 of 24 studies, no studies masked participants to the intervention assignment, and masking of outcome assessment was not done in 12 studies and was unclear in 12 studies.
Artificial pancreas systems uniformly improved glucose control in outpatient settings, despite heterogeneous clinical and technical factors.
Editorial - first segment
Artificial pancreas research: you can observe a lot by watching
Steven J RussellEmail the author Steven J Russell
Artificial pancreas systems combine continuous glucose monitors, computer algorithms, and drug pumps to make automated adjustments to therapy for patients with type 1 diabetes. The synergy of these components has the potential to improve glycaemic control while simultaneously reducing the burden of diabetes management on patients and caregivers. All artificial pancreas systems either partly or fully automate the delivery of insulin (single hormone) and several systems also automate the delivery of microdoses of glucagon (dual hormone) to prevent or treat hypoglycaemia when decreasing or suspending insulin delivery alone is insufficient. For more text pay to the editor
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