Recent insulin advancements improve diabetes management
Recent technology advances that help guide insulin dosing based on pattern recognition have fundamentally changed diabetes management for both patients and providers, and more “smart” improvements are on the horizon, according to a speaker.
“It has been exciting the last couple of years since we are finally getting the various automated insulin delivery systems into our patients’ hands, largely thanks to the FDA’s proactive stance as well as the introduction of the new regulatory categories encouraging interoperability, along with impressive growth in personal continuous glucose monitor use in my practice,” George Grunberger, MD, FACP, MACE, chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan, told Healio. “All of this has totally changed the approach to management of patients on intensive insulin regimens — and more improvements are coming. The second major development has been, finally, broad acceptance of telemedicine due to reimbursement of such visits during the COVID-19 pandemic. This allows for more efficient management for patients who have the ability to use and access technology — not givens, of course, in our dysfunctional health care delivery system.”
‘Smart’ pen solutions
Insulin delivery has changed dramatically since the days when Grunberger watched his grandfather sterilize a glass syringe and steel needle, which had to be sharpened daily to lessen the pain of animal-derived insulin injections.
“Now, we are entering the era of smart insulin pens,” Grunberger said during an online presentation at the virtual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “Until now, the problem has been that when the patient injects insulin, we don’t know how much insulin he or she injected, what time it was injected, and other things easily forgotten.”
Currently, the InPen (Companion Medical) is the only smart insulin pen available in the U.S. The pen, which transmits dosing data with Bluetooth technology and allows for programming of carbohydrate ratios and sensitivity factors, has simplified management for clinicians, Grunberger said.
“You can look at a ‘report card’ and make some sense of the glucose excursions,” Grunberger said. “Now it is easier to manage patients more carefully.”
Insulin delivery algorithms
A fully closed-loop insulin delivery system, sometimes called an artificial pancreas, remains out of reach today; however, hybrid closed-loop systems have helped simplify care for people with type 1 diabetes, even though carbohydrates must still be entered manually before a meal, Grunberger said. There are three available “brains” behind the currently available hybrid closed-loop insulin delivery systems in the U.S. market: proportional-integral derivative control, or PID; model predictive control, or MPC; and fuzzy logic control, or FL.
“They all work and there are fans in every corner, depending on whose side you are on,” Grunberger said. “Different systems use different ‘brains,’ but what is the point? What are you trying to achieve? Hopefully, good glucose control with as little variability as possible, keeping patients out of hyperglycemia.”
To determine what success looks like, researchers convened an international consensus meeting on time-in-range in Berlin in 2019. There, researchers agreed that time spent in the recommended glucose range, or time-in-range, is the “key metric,” defined as 70 mg/dL to 180 mg/dL.
“At least 70% of the time spent in this range constitutes a mark of success,” Grunberger said. “Now, we have metrics. Before, it was all about HbA1c.”
Advanced hybrid closed-loop insulin delivery is on the way, Grunberger said. The Medtronic 780G, approved in Europe but not yet in the U.S., can deliver a correction bolus automatically when a patient is about to enter hyperglycemia. In December 2019, the FDA authorized marketing of the Tandem Diabetes Care Control-IQ interoperable, automated insulin dosing algorithm, the first dosing controller that can be used with other interoperable diabetes devices.
The tubeless Omnipod 5 automated insulin delivery system (Insulet), which can be paired with the Dexcom G6 or the FreeStyle Libre CGM, is also in development, Grunberger said.
“The system that will hopefully get before regulators is the one where users can choose their own target,” Grunberger said. “This is what we have today on the market or coming soon.”
Non-injected insulin options
An oral insulin capsule is in development by Oramed Pharmaceuticals. In February, the company reported safety and efficacy results from the final cohort of its phase 2b trial, showing that the lead oral insulin candidate, ORMD-0801, met its primary endpoint demonstrating that participants with type 2 diabetes who received once-daily and twice-daily 8 mg doses achieved statistically significant reductions from baseline in HbA1c. The company announced in November that a phase 3 study is underway.
“The holy grail has always been not injecting insulin,” Grunberger said. “It’s tricky, because you have to ‘coat’ that insulin so it doesn’t get chewed up by gastric juices, protect it, and eventually get some absorption enhancers to make sure you get the biological effect.”
If the phase 3 study is successful, Oramed plans to submit the drug to the FDA by 2023, he said.
“It’s been a fascinating ride to see what has happened since 1921,” Grunberger said. “Different modalities and ways to introduce insulin into our bodies to not only live, but live without fear of hypoglycemia, and improve quality of life and those dreaded diabetes complications.”
Editor's note: This article was updated on Jan. 4, 2021, to state that the Medtronic 780G, approved in Europe but not yet in the U.S., can deliver a correction bolus automatically when a patient is about to enter hyperglycemia.
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Grunberger G. State of the art insulin delivery systems. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 3-6, 2020 (virtual meeting).
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