Glycemic Control Improved With Artificial-Pancreas Systems: Meta-Analysis

Miriam E Tucker

June 02, 2017

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 (< .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 (< .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%, = .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, = .08), although insulin doses were significantly higher with the artificial-pancreas systems in children (< .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.

Dr Russell also points out that a rather ironic notable omission from this meta-analysis is the Medtronic 670G, which was approved by the US Food and Drug Administration based on a nonrandomized safety trial with no controls, so it didn't qualify for inclusion.

According to Dr Weisman, the device — 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."

Dr Weisman has no relevant financial relationships. Disclosures for the coauthors are listed in the paper. Dr Russell has received personal fees and nonfinancial support from Abbott Diabetes Care; lecture fees from Sanofi; lecture fees, personal fees for sitting on the scientific advisory board, and nonfinancial support from Tandem Diabetes Care; nonfinancial support and lecture fees from Eli Lilly; nonfinancial support from Dexcom; nonfinancial support from Sweet Spot Diabetes; nonfinancial support from Nova Biomedical; lecture fees from Novo Nordisk; a grant and donation of study drug from Zealand Pharma; nonfinancial support Senseonics; and nonfinancial support from Xeris Pharma. He has a patent application related to aspects of glucose control with a bionic pancreas (single-hormone and dual-hormone configurations) licensed to Beta Bionics. He is on the scientific advisory boards for Companion Medical and Tandem Diabetes Care.

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Lancet Diabetes Endocrinol. Published May 19, 2017. Abstract, Editorial

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