Some automated insulin delivery systems currently in development add glucagon and/or pramlintide to insulin, but whether the extra hormones are worth the additional cost and effort is a subject of debate.
Sara Freeman/MDedge News
Dr. Roman Hovorka
Also called closed-loop or artificial pancreas systems, they are comprised of an insulin pump and a continuous glucose monitor (CGM) that communicate via a built-in algorithm to deliver insulin based on glucose levels. Currently available systems are called hybrid closed loops because they still require user input for meals, exercise, illness, and other special circumstances.
Two hybrid closed-loop systems available in the United States, the Medtronic Minimed 670G and the Tandem Control-IQ, as well as the Medtronic Minimed 780G that was just approved in Europe, use insulin only.
Of all ongoing active closed-loop clinical studies, 44 involve insulin-only systems, as of May 2020.
However, two such systems in development add a glucagon analogue to insulin in the same pump (in separate cartridges), with the aim of minimizing the risk of hypoglycemia. And four investigational systems combine insulin with pramlintide (Symlin, AstraZeneca), an amylin analogue that reduces postmeal glucose spikes. Three systems in development combine all three hormones.
In a debate during the virtual American Diabetes Association 80th Scientific Sessions, Roman Hovorka, PhD, of the University of Cambridge (England) argued in favor of insulin-only systems on the basis of efficacy, less burden and complexity, and lower cost.
But Steven J. Russell, MD, PhD, of Massachusetts General Hospital, Boston, countered that glucagon adds safety and value to the system by allowing for more aggressive insulin dosing with lower hypoglycemia risk, benefits which he said would overcome any downsides.
Insulin-only systems are good enough
Dr. Hovorka began by defining a “good” artificial pancreas as one that produces consensus time-in-range targets of at least 70% of glucose values between 3.9 to 10 mmol/L (70-180 mg/dL) and less than 3% below 3.9 mmol/L (70 mg/dL). At the same time, he said, the burden should be low, which he suggested means no more than 10-20 minutes a day spent managing the system, low “alarm burden,” and minimal technical issues.
“We need to balance glucose control and the burden. For some people, reducing the burden is sometimes even more important than the glucose control,” Dr. Hovorka commented.
He pointed out that, in addition to Medtronic’s and Tandem’s systems, two other insulin-only hybrid closed-loop systems are marketed outside the United States. These are the CamDiab system, available in the United Kingdom, which uses his group’s Cambridge control algorithm in a Dana pump with the Dexcom G6 sensor, and the Diabeloop algorithm, available in Europe, that combines a patch pump with the Dexcom G6.
“Lots of energy and resources are going to taking [insulin-only] systems into clinic use,” Dr. Hovorka observed.
He reviewed recently published data for both the Tandem Control-IQ and the Cambridge control algorithm showing similar results meeting the “good artificial pancreas” definition.
In his current clinic population of 160 patients aged 2-80 years using the Cambridge algorithm, 69% of users have achieved 70% or greater time in range and 28% have achieved 80% or greater time in range.
“So, the insulin-only system can achieve acceptable, and in some instances very good, glucose control,” Dr. Hovorka said.
He acknowledged that there are still challenges with insulin-only systems, including exercise-related dysglycemia and postprandial hyperglycemia related to slow insulin absorption, missed or incorrect boluses, or large meals.
But, Dr. Hovorka said, downsides of dual-hormone systems include the need for room-temperature stable glucagon and for dual-chamber pumps with two cannulas and two infusion sites (in addition to the sensor site), and the unknown long-term biological risks of chronic subcutaneous glucagon or pramlintide delivery.
Moreover, he said, costs are expected to be higher for a two-chamber versus single-chamber pump, as well as for the second hormone, reservoir, and infusion set.
Data thus far from short-term studies suggest that insulin-only systems are sufficient in eliminating nocturnal hypoglycemia, while the addition of glucagon potentially reduces daytime hypoglycemia, especially during exercise.
However, longer-term head-to-head studies will be needed, Dr. Hovorka said, noting, “Comparative benefits of the single- and dual-hormone system for improving hemoglobin A1c and preventing severe hypoglycemia remain unknown.”
He suggested that glucagon dual-hormone closed-loop systems might be suitable for patients who are particularly prone to hypoglycemia, whereas pramlintide dual-hormone systems have the potential to more fully close the loop when used with ultra rapid-acting insulin analogues.
Nonetheless, he said, “Many, if not most, users may achieve acceptable control with insulin-only systems.”