May 2020 Issue
Insulin Delivery Devices in 2020 and Beyond
By Hope Warshaw, MMSc, RD, CDE, BC-ADM, FADCES
Vol. 22, No. 5, P. 28
New innovations and technologies are lessening the burden of diabetes self-care, enabling people to attain a higher quality of life.
Did you know that the year 2021 will mark 100 years since the discovery of insulin?1 Until the 1970s, when the first insulin pump (continuous subcutaneous insulin infusion [CSII]) became available, everyone took insulin via syringes and vials.2 The first traditional insulin pens, devices that simply deliver insulin, became available in 1985. Fast-forward to 2020. Today, people who use insulin have more choices about how they take it than ever before. And more innovation, particularly systems that make insulin delivery devices more integrated and interoperable, is just around the corner.
Step by step, technological capabilities have enabled this evolution, including “the single largest innovation in diabetes care of late, continuous glucose monitoring (CGM) technology,” says Jamie Kowatch, MS, RD, CDE, of Saluté Nutrition, PLLC, in Seattle, who’s had type 1 diabetes for 30 years, and uses t:slim X2 and Dexcom G6 CGM.
Today, an increasing number of insulin delivery devices wirelessly transmit real-time or intermittently scanned CGM data (depending on the CGM device used). These integrated systems offer opportunities for people with diabetes and their clinicians to more easily detect management challenges and evolve care more effectively and time-efficiently.
Back to Reality
Statistics from the Centers for Disease Control and Prevention estimate that 7.4 million Americans take insulin.3 Of this number, 1.6 million Americans have type 1 diabetes and require insulin. From these estimates, one can interpolate that about 6 million Americans with type 2 diabetes take insulin. A surprising minority—30% of people with type 1 and less than 1% of people with type 2—use CSII.4 Interpolating again, about 2 million people with diabetes use multiple daily injections (MDI), typically one to two injections per day of long-acting (basal) insulin and rapid-acting (bolus) insulin to manage glycemic excursions from meals, snacks, and, at times, elevated glucose levels.
Despite the development and availability of more sophisticated insulin delivery devices, the majority of people continue to use syringes and vials or traditional insulin pens. The question is, why? “Many people are intimidated by new technology or worried they can’t afford it,” says Kayleigh Mouat, RD, with the endocrinology group at Witham Adult Medical Specialists in Lebanon, Indiana. “However, if people with diabetes are open-minded, we can almost always find a technology-based insulin delivery solution to fit their needs, improve clinical parameters, and lower the burdens of self-care.”
RDs with knowledge of the full spectrum of insulin delivery devices currently available in the US marketplace and who have a glimpse of what’s coming soon can present more options to people with diabetes they counsel. “Most people with diabetes are willing to try new devices if their provider spends sufficient time showing them what the devices look like and how they work,” says Bettina Engh, APRN-BC, RD, an endocrinology nurse practitioner and dietitian at Frist Clinic in Nashville. “Just handing out pamphlets or giving links to websites isn’t helpful.”
Clinicians typically underestimate the day-to-day challenges of taking insulin. For starters, “Just remembering to take insulin doses is an understandable challenge for many,” Kowatch says.
Then there’s proper insulin dosing technique, “a requisite to obtain the full benefits of insulin injection therapy.”5 Add to this, particularly for those on MDI, keeping constant track of insulin action curves. They must balance these with the unpredictability of life, meal and snack times, physical activity, stress, illness, sleep, and more.
It’s critical for people with diabetes to monitor their insulin doses along with tracking other essential data they and their clinicians need to assess their care plan and make adjustments. And they need to integrate all of these diabetes self-care steps into an already busy life.
Newer Devices Offer Assists
The legacy insulin delivery devices (ie, syringes and traditional pens) don’t do much to decrease diabetes self-care burdens. However, traditional pens in place of syringes and vials have been found to increase dosing accuracy, be more convenient and easier to use, improve adherence to taking insulin, and increase satisfaction.2,6
Newer, and particularly the technology-enabled, insulin delivery devices detailed in the following section can help people overcome even more challenges to taking insulin. These devices can record all data, along with insulin doses and time of delivery, offering ease of data analysis. They also can track insulin-on-board (the amount of active rapid-acting insulin still working based on a set duration of action) to minimize potential hypoglycemia. The CSII management systems offer the greatest flexibility to deliver insulin to cover food and elevated glucose levels and increase or decrease basal insulin as needed. And, as CSII management systems become more automated (see sidebar “Closer to Closing the Loop”), the delivery of more or less insulin based on glucose levels will be managed independently by the system based on targets set by the user and their clinicians.
An array of insulin delivery devices have been cleared or approved by the FDA (see sidebar “FDA Review Processes Evolve”). What follows are key details of most of the devices available today in the United States. However, the list isn’t exhaustive and doesn’t include devices in other parts of the world that aren’t available in this country.
Several overlapping themes permeate ongoing innovation. One is forging partnerships. Another is enabling data integration and analysis, which usually involves a CGM manufacturer. The third theme is interoperability between system components to offer choice and customization.
Device Category: Inhaled Insulin
Product name: Afrezza
Description: Cartridges of ultra-rapid-acting insulin in 4U, 8U, and 12U are placed in the device and inhaled for mealtime doses (bolus). Used in combination with basal (long-acting) insulin. (Note: Units of this insulin aren’t equivalent to units of U100 insulin.) Before starting Afrezza, get a baseline FEV1 (forced expiratory volume in 1 second) test.
FDA status and ages for intended use: Approved as a new drug in 2014; people aged 18 and older who take insulin, use not indicated in people with COPD and asthma.
Assets: Eliminates bolus injections, quick acting, ultra-rapid-acting (unique to Afrezza), has speed of onset of 12 minutes, duration of action 60 to 90 minutes.
Data integration/management platform/app: BluHale professional edition, personal edition in future integration with Glooko (data management platform) and Dexcom.
Device Category: Smart Insulin Pen
Manufacturer: Companion Medical
Product name: InPen with diabetes management app system
Description: Durable (reusable) pen, uses prefilled 300U cartridge of U100 rapid-acting insulin (Fiasp, Humalog, or NovoLog), delivers bolus doses from 0.5U increments up to 30U.
FDA status and ages for intended use: Cleared in 2016 for people aged 12 and older.
Assets: Reminds users of missed doses (bolus and basal), autoprime detection, dose calculator based on individualized therapy settings similar to CSII, and records all data.
Data integration/management platform/app: Data wirelessly transmits via Bluetooth to InPen app, integrates with Dexcom CGM and Bluetooth-enabled BGMs, provides InPen Insights integrated sharable data report.
Device Category: Simple Patch
Product name: CeQur Simplicity (Pilot launch 1H2020, scaled launch overtime)
Description: Three-day wearable, disposable patch that user fills with 100U rapid-acting insulin (Humalog or NovoLog) with 100U to 200U mealtime (bolus) dosing. Each patch comes with a syringe to fill and a reusable inserter.
FDA status and ages for intended use: Cleared in 2010 for adults who take insulin.
Assets: Convenient, discreet, eliminates mealtime injections (bolus doses).
Data integration/management platform/app: None
Device Category: Simple Patch
Product name: V-Go
Description: Patch with inserter that simplifies MDI (basal/bolus) therapy, user fills with rapid-acting insulin (Humalog or NovoLog), device changed every 24 hours, patch available in 20U, 30U, or 40U for basal dosing, bolus available on demand in 2U increments.
FDA status and ages for intended use: Cleared in 2010 for individuals aged 21 and older who require insulin.
Assets: Discreet, eliminates multiple injections each day.
Data integration/management platform/app: Launching Bluetooth accessory named V-Go SIM (2H2020).
Device Category: Insulin Pumps and Pod
Manufacturer: Insulet Corporation
Product name: Omnipod DASH Insulin Management System
Description: Insulin delivered via filled tubeless pod (up to 200U) with automatic insertion; communication with pod is through locked-down Android device.
FDA status and ages for intended use: Cleared in 2018 for all individuals.
Assets: Waterproof, discreet insulin delivery, not considered durable medical equipment; covered under Medicare Part D, supplies available at pharmacies, lower upfront cost compared with other pump systems.
Data integration/management platform/app: Bluetooth wireless technology syncs with Contour Next1 BGM. Two apps: Omnipod DISPLAY and VIEW, and iPhone widget that allows viewing of insulin and CGM data on one screen. VIEW allows loved ones and caregivers to remotely monitor the user on their smartphones. Omnipod DASH System allows viewing of data using Glooko.
Device Category: Insulin Pumps and Pod
Product name: MiniMed 670G
Description: Hybrid closed loop system (functions partially automated but still requires bolus doses for meal/food); in auto mode, it automatically adjusts basal insulin every five minutes based on CGM results and assists with under- or overestimation of carbohydrate intake; suspends insulin up to 30 minutes before reaching preset low limits, automatically restarts when glucose level recovers, holds up to 300U rapid-acting insulin, comes with integrated CGM (Guardian Sensor 3) and BGM Contour Next Link (wirelessly connects).
FDA status and ages for intended use: Approved in 2017 for individuals aged 7 and older.
Assets: Waterproof pump holds 90 days of pump history, insulin delivery can be in low basal and bolus delivery increments.
Data integration/management platform/app: CARELINK software integrates all data.
Device Category: Insulin Pumps and Pod
Manufacturer: Tandem Diabetes Care
Product name: t:slim X2 with Control-IQ (t:slim X2 also available alone or with basal IQ).
Description: Predicts and helps prevent hypoglycemia and hyperglycemia with use of CGM (Dexcom G6) data, can decrease or stop basal insulin to hold glucose in range of 70 to 180 mg/dL, auto-correct bolus doses, optional settings for sleep and exercise.
FDA status and ages for intended use: Cleared in 2019 for people aged 12 and older.
Assets: Unique, free updatable software uploads for next generation with prescription; training and online tutorials required.
Data integration/management platform/app: Integrated with Dexcom G6 CGM, t:connect portal, app in beta testing.
More than ever, innovation promises to continue at a faster pace. What was once thought to be impossible to achieve will become possible. “I’m more excited about how the device and technology companies are pushing each other than a specific technology on the horizon,” Kowatch says.
Optimal data integration and device interoperability will become paramount with an essential goal to minimize the load of managing a burdensome disease. “I love the idea of being able to ignore my diabetes more!” Kowatch says.
To stay current on this quickly evolving area, RDs should “befriend the sales and clinical representatives from the various companies,” Mouat says. If dietitians are curious about a manufacturer’s next-generation product, they should visit the investor page on the company’s website (if it’s a public company). They can speak with colleagues who specialize in diabetes, particularly those who counsel people who take insulin. And they can seek out continuing education programs or professional meetings that offer a deep dive into insulin delivery devices.
— Hope Warshaw, MMSc, RD, CDE, BC-ADM, FADCES, is owner of Hope Warshaw Associates, LLC, a diabetes- and nutrition-focused consultancy based in Ashville, North Carolina. She’s the author of numerous books published by the Association of Diabetes Care & Education Specialists (formerly AADE). Warshaw served as the 2016 president of ADCES and currently serves on the board of the Academy of Nutrition and Dietetics Foundation.
Hope Warshaw, MMSc, RD, CDE, BC-ADM, FADCES, reports the following relevant disclosure: She currently provides consulting services for Companion Medical and Tandem Diabetes Care.
1. This history of a wonderful thing we call insulin. American Diabetes Association website. https://www.diabetes.org/blog/history-wonderful-thing-we-call-insulin. Updated January 8, 2020. Accessed February 11, 2020.
2. Selam JL. Evolution of diabetes insulin delivery devices. J Diab Sci Technol. 2010;4(3):505-513.
3. Centers for Disease Control and Prevention. National diabetes statistics report, 2020. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed February 11, 2020.
4. Sikes KA, Weyman K. Diabetes and the use of insulin pumps. Endocrinology Advisor website. https://www.endocrinologyadvisor.com/home/decision-support-in-medicine/endocrinology-metabolism/diabetes-and-the-use-of-insulin-pumps/. Accessed February 11, 2020.
5. American Diabetes Association. 7. Diabetes technology: standards of medical care in diabetes - 2020. Diabetes Care. 2020;43(Suppl 1):S77-S88.
6. Sangave HA, Aungst TD, Patel DK. Smart connected insulin pens, caps and attachments: a review of the future of diabetes technology. Diabetes Spectr. 2019;32(4):378-384.
CLOSER TO CLOSING THE LOOP
Several automated insulin delivery (AID) devices, also called closed-loop systems, are expected to receive FDA approval in late 2020 or early 2021. AID is the preferred term over the misnomer artificial pancreas, or as Jamie Kowatch, MS, RD, CDE, of Saluté Nutrition, PLLC, in Seattle, puts it, “the ‘technological’ vs ‘physiologic’ cure.”
Dietitians will see closed-loop systems from companies currently in the insulin delivery device business as well as other entities. This trajectory is in sync with process changes and innovation at FDA (see sidebar “FDA Review Processes Evolve” on page 31).
• Beta Bionics is working to bring the iLet to market. It’s a pocket-sized, dual-chamber (one holds insulin, the other holds liquid-stable glucagon), autonomous, glycemic control system intended to mimic a biological pancreas. (Currently, there’s no FDA-approved liquid-stable glucagon.)
• Bigfoot Biomedical is designing a complete package solution for people with diabetes who take insulin, which includes the needed devices, software, and services that will enable people to take insulin more safely and cost effectively.
• Insulet is completing its pivotal study, required for FDA submission, for its AID system Omnipod HORIZON, described as an Automated Glucose Control System run with a personal smartphone.
• Medtronic is working on the MiniMed 780G, designed to automate insulin delivery in a real-time, adaptable way while also providing predictive diagnostics personalized for each user.1 It’s described as an advanced hybrid closed-loop system that will be Bluetooth compatible and receive wireless updates.
• Tandem, closer to closing the loop than others with its recent FDA approval of t:slim X2 with Control IQ, continues to forge ahead with the t:sport, a discreet tubed pump, referred to as a micropump. It won’t have a screen; users will control the device with their mobile phone. The t:sport will incorporate an alternate controller-enabled insulin pump (referred to as an ACE pump) intended to infuse insulin.
1. Medtronic receives FDA breakthrough designation for developing personalized closed loop insulin pump system for diabetes management. Medtronic website. http://newsroom.medtronic.com/news-releases/news-release-details/medtronic-receives-fda-breakthrough-designation-developing. Published February 19, 2019. Accessed February 11, 2020.
FDA REVIEW PROCESSES EVOLVE
The FDA, specifically the Center for Devices and Radiological Health (CDRH), is making ongoing changes to how it categorizes and classifies medical devices for diabetes management due to the evolving sophistication of insulin delivery devices and the drive toward automated insulin delivery systems.1
For background, the FDA reviews all medical devices according to their classification before giving them the green light to enter the marketplace. Class I devices present minimal potential harm to the user. Class II devices, such as older continuous subcutaneous insulin infusion (CSII) systems, can present moderate risk. Class III devices, such as the newer CSII systems, can present high risk to the user. For Class I and II devices, manufacturers submit a Premarket Notification (known as 510k). Upon FDA review, manufacturers receive “clearance” to market the device. For Class III devices, a Premarket Approval Application, involving a more rigorous review, is required to demonstrate safety and efficacy. Insulin delivery devices and insulin delivery systems are referred to as “approved.”
In early 2019, the CDRH made changes to enable faster innovation, less regulatory burden, more component flexibility, and more choices for people with diabetes.1,2 The FDA defined new categories and a new De Novo Premarket Review pathway that includes an interoperable automated glycemic controller device (referred to as iController) that automatically adjusts insulin delivery by connecting to an alternate controller-enabled insulin pump (called an ACE pump) and integrated continuous glucose monitoring (called iCGM). The ACE pump is a device intended to infuse insulin and may include basal and bolus drug delivery at set or variable rates. It’s designed to reliably and securely communicate with external devices, such as an automated drug-dosing system that enables drug delivery commands to be received, executed, and confirmed. These changes are paving the way for interoperability—the ability to purchase different components, based on device preferences, and avoid purchasing the complete system from only one manufacturer. To date, the t:slim X2 with Control-IQ was the first device the FDA approved to go through this new De Novo Premarket Review pathway.3
In addition, in early 2019, the FDA designated another new review pathway, the Breakthrough Devices Program, which provides priority review to help people gain access to breakthrough technologies faster.1,4 Medtronic received this designation for its next-generation system.
1. Reorganization of The Center for Devices and Radiological Health. FDA website. https://www.fda.gov/about-fda/center-devices-and-radiological-health/reorganization-center-devices-and-radiological-health. Updated May 1, 2019. Accessed February 11, 2020.
2. Consumers (medical devices). FDA website. https://www.fda.gov/medical-devices/resources-you-medical-devices/consumers-medical-devices#How_are_Medical_Devices_Classified. Updated April 9, 2019. Accessed February 11, 2020.
3. FDA authorizes first interoperable, automated insulin dosing controller designed to allow more choices for patients looking to customize their individual diabetes management device system. FDA website. https://www.fda.gov/news-events/press-announcements/fda-authorizes-first-interoperable-automated-insulin-dosing-controller-designed-allow-more-choices. Updated December 13, 2019. Accessed February 11, 2020.
4. Schaffer R. FDA expedites new insulin pump technology with device approvals. Endocrine Today website. https://www.healio.com/endocrinology/bone-mineral-metabolism/news/print/endocrine-today/%7B864c087d-46ba-462c-b13c-106ca2dca557%7D/fda-expedites-new-insulin-pump-technology-with-device-approvals. Published April 2019. Accessed February 11, 2020.
DIY AUTOMATED INSULIN DELIVERY
The do-it-yourself (DIY) automated insulin delivery (AID) systems have been developed, assembled, and supported by technology-savvy people with type 1 diabetes or their loved ones since ~2015.1,2 Instigated by the #wearenotwaiting movement and the goal to obtain a better quality of life, use of these systems has snowballed among people tired of waiting for manufacturers and the FDA to get AID systems on the market. DIY systems (two in use) require a compatible insulin pump (either an older model Medtronic pump or older Omnipod system), continuous glucose monitoring (CGM), and a small computer or circuit board that communicates. When up and running, the small computer or circuit board uses CGM data and information about previous insulin dosing and carbohydrate consumption. From these data, it develops forecasts for what glucose levels are likely to do over time. Data are sent to the pump or pod, which then inputs a revised temporary insulin delivery rate up to every five minutes.
These systems can’t be purchased and are unsupported by customer service. People who use them put them together on their own with manuals and support from the global community of DIY users. Clinicians who encounter people with diabetes wanting to or who already use a DIY system have unique challenges. “As with any non–FDA-approved therapy, I make sure the people with diabetes know this is off-label. I discuss the risks and benefits and document all of this in my notes,” says Bettina Engh, APRN-BC, RD, an endocrinology nurse practitioner and dietitian at Frist Clinic in Nashville.
1. Lewis DM. Do-it-yourself artificial pancreas system and the openAPS movement. Endocrinol Metab Clin North Am. 2020;49(1):203-213.
2. Weedman BJ. You built a what?! Do-it-yourself automated insulin delivery systems. AADE in Practice. 2019(Sept);24-31.