If you pay attention to diabetes news at all, you’ve surely heard the terms “Artificial Pancreas,” “closed loop system,” or “bionic pancreas” a lot in recent years. And if you live with diabetes yourself, family and friends may even be asking if you have one of these yet.
This futuristic technology is now officially being referred to as AID (Automated Insulin Delivery) systems, and they are getting very close to truly changing the game for people whose lives depend on insulin.
To date, the Food and Drug Administration (FDA) has approved two early commercial AID systems, the Medtronic MiniMed 670G and Control-IQ from Tandem Diabetes Care. Other companies are working on versions that may be available soon.
Meanwhile, a vibrant D-patient do-it-yourself (DIY) community has been developing their own homemade versions that are becoming widely used across the country.
Although Artificial Pancreas (AP) sounds like a single appliance that you would just plug into your body, the fact is: we are not there yet.
It’s taken researchers decades to connect various diabetes devices using a combination of cables and wireless technology and creating a system that can mimic what a healthy pancreas does: monitor glucose levels and deliver insulin as needed.
Currently, an AP is essentially an insulin pump connected to a continuous glucose monitor (CGM). The monitor is controlled via a receiver (currently a separate handheld device, but in the future could be a smartphone mobile app) using sophisticated software algorithms to make the whole thing work.
The idea is to automate blood glucose (BG) control as much as possible, so the wearer no longer has to take fingerstick blood sugar readings and then calculate how much insulin to dose or reduce based on readings. Some systems can even shut off insulin delivery automatically based on low blood sugar readings detected by the CGM. And some systems are experimenting with carrying glucagon in the pump alongside insulin, to bring blood sugar up when necessary.
These systems are at various points in development, from clinical studies to early commercial products to those “hacked” into by tech-savvy DIYers who don’t want to wait for FDA-approved products. Incredible strides are being made, and new groups and companies seem to be emerging to work on this exciting advancement in diabetes technology.
Products included in current AP systems:
- an insulin pump, which provides a continuous flow of insulin into the body via an “infusion site” or small cannula inserted in the skin
- a CGM that takes ongoing blood sugar readings via a little sensor worn on the skin that has its own separate cannula from the pump. There are currently two traditional CGMs on the market in the U.S. from Dexcom and Medtronic that offer high and low alerts continuously as part of the device functionality.
- a controller — either the insulin pump itself or a separate receiver; eventually a smartphone mobile app — that includes the display screen where users can see glucose data
- algorithm software, the “brain” of the system, that crunches the numbers to predict where glucose levels are headed and then tells the pump what to do
- glucagon, a hormone that rapidly increases blood glucose, used here as an antidote to hypoglycemia (low blood sugar)
The full retail price for the Medtronic 670G system is between $7,000 to $8,000. But with insurance coverage, most patients pay just over $1,000 to initially get on the system, and then must pay for pump and CGM supplies on an ongoing basis. The annual cost of the CGM transmitter is $699, and sensors run from $50 to $75, depending on the amount purchased. Medtronic offers financial assistance to patients in need.
The newer Tandem Control-IQ system is being offered as a free software update for in-warranty t:slim X2 pump users in the U.S. who purchase the pump before December 31, 2020. Existing users can access the upgrade through the Tandem Device Updater, which is simply plugged into a computer with a micro-USB cable.
Outside of that free offer, the cost of the Tandem t:slim X2 pump with Control-IQ is $4,000, but Tandem says health insurance typically covers 80 percent of that cost.
But, you still need to purchase all the Dexcom G6 CGM supplies separately. While insurance coverage may vary, the retail price would be $237 for a single G6 transmitter that lasts three months and $349 for a box of three 10-day sensors.
Some new AP systems are expected to hit the market by mid to late 2021, with many options to follow in the next few years.
Specific price tags for newer systems are not yet available, but should not exceed the cost of the insulin pump and CGM currently used. Some companies, notably Bigfoot Biomedical, are even working on a “package” subscription model that will offer the user all the supplies they need on a monthly basis for one monthly payment.
There is no single inventor to thank but rather a whole host of companies working on developing a market-ready AP system. They include, in alphabetical order:
Born out of the University of Boston iLet Bionic Pancreas Project, Dr. Ed Damiano and team have been working on Beta Bionics for more than a decade. Animal trials took place in 2005, human trials began in 2008, and it’s continuing to evolve today. In 2016, the “Go Bionic” team formed a commercial public benefit corporation to develop and bring their iLet system to market. This dual-chambered device with a sophisticated user interface will include pre-filled cartridges of insulin and glucagon to eliminate the need for manual filling by the user. It is expected to be released by 2022.
Established in late 2014 by former JDRF CEO Jeffrey Brewer and a group of D-Dads, Bigfoot hired some of the most prominent AP entrepreneurs and purchased the intellectual property from now-defunct insulin pump company Asante Solutions. They have teamed up with Abbott Diabetes Care to use a next-generation FreeStyle Libre Flash monitoring system with their system. Bigfoot also acquired Timesulin to create a smartpen version of their automated insulin delivery (AID) system, alongside the pump version. The company received the FDA’s expedited “breakthrough device designation” in November 2017 and filed its “Bigfoot Unity” pen version with the FDA in mid-2020. You can read the origin story here.
Diabeloop is a European pump company and French research consortium developing and testing new AP systems in the United Kingdom and France. It was using the Kaleido hybrid patch-tubed pump in its first developed version, but since that device has been discontinued Diabeloop has been working to integrate other pump technology — such as the Roche Accu-Chek system.
The leading CGM sensor technology from the San Diego-based Dexcom is at the heart of a large majority of AP systems under development, including some DIY systems being cobbled together by citizen hackers. To enable further development, Dexcom integrated an AP algorithm into their G4 product in 2014, and has signed device integration agreements with insulin pump makers Insulet (Omnipod). The latest G6 and future G7 models will be used in closed loop systems with Tandem’s t:slim X2, Insulet’s Omnipod 5 (formerly the Horizon), and more. In 2018, the CGM company acquired closed loop startup TypeZero Technologies with plans to offer those algorithms as an option to D-Tech companies going forward.
Dose Safety is a Seattle-based startup developing a sophisticated controller for use in AP systems.
DreaMed Diabetes is an Israel-based startup established in 2014 as a spinoff of the DREAM International Consortium in order to commercialize the AP technology behind its Glucositter software. In 2015, Medtronic signed an agreement to use Glucositter in its future closed loop technology. It uses an algorithm based on a “fuzzy logic” theory, which is a learning algorithm meant to minimize the risks of hypo/hyper events.
EoFlow is a South Korean company developing an AID system dubbed EoPancreas. This uses the “EoPatch” patch pump available in Asia that will be integrated with a CGM sensor made by China-based POCTech. Eventually, the company hopes to build in other CGMs. It will use an Android phone-style, locked-down controller similar to the controller used by the most recent version of the Omnipod tubeless insulin pump. The control algorithm will be one previously licensed by TypeZero Technologies. EoFlow received the FDA’s “breakthrough device designation” in March 2019.
Insulet Corp. is a Boston-based manufacturer of the tubeless Omnipod insulin pump. It announced integration with the Dexcom CGM in 2014, and later struck a deal with AP software firm Mode AGC (Automated Glucose Control LLC) to develop and incorporate their advanced AP algorithm in the system. It’s developing the Omnipod 5 (formerly known as the Omnipod Horizon), and it’s anticipated in mid-2021.
Lilly Diabetes, an Indianapolis-based pharma-giant insulin-maker, has been working on its own AID system. The company had been jointly developing its own pump delivery system, but in 2020 scrapped that project to instead commercialize the European-made YpsoPump in the U.S. Aside fron that pump AID cersion, Lilly is developing a connected insulin pen system. The company is collaborating with Dexcom on the CGM side.
Medtronic Diabetes is the insulin pump market leader and only company that manufactures both a pump and CGM device. It famously launched its combo system with low-glucose suspend (530G) in 2014, the first product approved through a new FDA designation intended to smooth the regulatory path for these devices. Medtronic also signed an exclusive agreement in 2015 to use AP software Glucositter in its future systems.
On September 28, 2016, Medtronic’s MiniMed 670G “hybrid closed loop” system was the first-ever FDA-approved system to automatically dose insulin based on CGM readings. It is therefore the first “early AP” on the market. Using the company’s fourth-generation CGM sensor called Guardian 3, it automatically adjusts basal (background) insulin to keep a user as close as possible to 120 mg/dL, limiting low and high blood sugars. In 2018, the FDA gave it a “pediatric indication” approval for use in kids as young as age 7.
Its next-generation system in the pipeline is the 780G, an “Advanced Hybrid Closed Loop” that will be more fully-automated and personalized with automatic bolusing and a lower target of 100 mg/dL. It will also be connected to the next-gen Zeus CGM sensor.
Pancreum is a visionary startup established by a former Insulet engineer who aims to create a three-part modular design to make the AP system more flexible and useful for patients.
Tandem Diabetes Care
Tandem Diabetes Care, makers of the innovative t:slim insulin pump, launched the second-ever FDA-cleared closed loop system, Control-IQ, in December of 2019. This is the most advanced commercial closed loop system available, leap-frogging Medtronic Diabetes’ first-to-market MiniMed 670G Hybrid Closed Loop that only adjusts background basal rates but doesn’t support automatic food or correction boluses. It is also the only Dexcom CGM-compatible system to date, since the Medtronic system works solely with that company’s own continuous sensor. Initial user feedback has been highly positive.
TypeZero Technologies began as a Charlottesville, Virginia-based startup that spun off from years of closed loop research and development of an AP system at the University of Virginia (UVA). Work focused on commercializing what the UVA originally called DiAs (Diabetes Assistant systems), and was first focused on integrating with the Tandem Diabetes closed loop technology. In 2018, CGM-maker Dexcom acquired TypeZero Technologies with plans to license those algorithms out to other players developing these AP systems.
Here’s the skinny on some of the key terminology involved:
Algorithms. An algorithm is a set of step-by-step mathematical instructions that solve a recurrent problem. In the AP world, there are a bunch of different approaches to this, which is a shame because standardizing the protocols and reporting metrics would be hugely beneficial to both physicians (for evaluating data) and patients (for getting access to systems that provide a choice of interchangeable components).
Closed Loop. An automatic control system in which an operation, process, or mechanism is regulated by feedback. In the diabetes world, a closed loop system is essentially an AP, where insulin delivery is regulated by feedback from an algorithm based on CGM data.
Dual Hormone. This is an AP system that contains both insulin and glucagon.
UI (user interface). A technology term that refers to everything designed into a device with which a human being may interact, such as the display screen, colors, buttons, lights, icon characters, help messages, etc. Researchers have come to realize that a poorly designed UI could prevent patients from using an AP system. Therefore, a great deal of effort is currently going into the design of the UI.
Low-Glucose Suspend (LGS) or Threshold Suspend. This feature allows an AP system to automatically shut down insulin delivery in the case that a low blood sugar threshold is reached. This capability is key to creating an AP that can truly control glucose levels.
Many in the D-Community are turning to DIY tech to create their own data-sharing tools and so-called AID. This tech-savvy movement is purely open-source, meaning the community is constantly co-developing the tools collectively by gathering on Facebook and at the developer site, GitHub. The technology can be revised as needed based on the work others are doing and how the apps are found to be functioning in the real world.
Some terms to know:
#WeAreNotWaiting: This hashtag has become a rally cry among citizen hackers moving ahead with medical device innovation without waiting for doctors, pharma, or the FDA to give them the go-ahead. This grassroots initiative has been very influential in accelerating innovation, including AP development.
#OpenAPS:This DIY AP system was created by citizen hackers Dana Lewis and Scott Leibrand. Their incredible work has spawned a movement, as more and more patient entrepreneurs begin to use and iterate on this system. The FDA has acknowledged OpenAPS, and is still grappling with how to respond.
#AndroidAPS: Largely the same as the above-mentioned OpenAPS, but based in Europe, with the technology running on Android smartphone devices.
Looping: Sometimes used as a general term for anyone using an open-source closed loop system, Looping also refers specifically to the Loop systems. These are apps that work with an insulin pump, RileyLink device (below) and iPhone. Read this overview of these systems.
RileyLink:A small device that serves as a “brain” for Loop systems. It connects an iPhone to a Dexcom CGM and insulin pump to create the Looping systems. It was developed by D-Dad Pete Schwamb and named after his daughter, Riley, who lives with type 1 diabetes. The official site for more information and ordering is GetRileyLink.org.
LoopDocs: This is an incredibly comprehensive online instruction guide on Looping, created by D-Mom Katie DiSimone who uses this DIY technology and keeps up on the latest developments. This resource also offers a range of other information that includes Facebook groups and other online tools to learn more and get involved.
Tidepool Loop: In 2018, the non-profit diabetes data platform startup Tidepool announced that it had obtained funding to start work on an “official” version of Loop that will be paired with the Omnipod insulin pump. This will take the DIY community version and build it into a product that can be reviewed by FDA through the official regulatory process for commercial availability. The organization hopes to file in late 2020 or early 2021, and the community is very anxious to see it materialize.
Research shows, in general, APs are safe and effective. However, just like any med-tech devices, these systems aren’t perfect. Out-of-range blood sugars can still happen, so users need to proceed with caution. That’s especially true for systems that are not FDA-regulated, as the algorithms are often still under construction.
In the Diabetes Online Community on blogs, Twitter, Facebook, and Instagram, there are countless examples of people using this diabetes technology successfully and sharing their experiences.
Two early trials that kicked off in January of 2016 helped pave the way for FDA approval of a commercial product by proving the safety and efficacy of an AP system over the long-term (6 months to a year) “in the patient’s natural environment.”
Here are some important facts about AP development.
FDA and JDRF are Pushing Hard on AP Progress
Actually, they’ve been pushing on this for over a full decade. Here’s a timeline:
Path to the AP: Back in 2006, JDRF established the Artificial Pancreas Project Consortium (APPC), a multi-year, multi-million dollar initiative to accelerate AP development. This got a big boost when that same year, FDA also named
Guidance: In March 2011, JDRF proposed that the FDA issue guidance to help further accelerate development. JDRF worked with clinical experts to draft those initial recommendations, which were released in December 2011.
First Clinical Trial: In March of 2012, the FDA gave the green light to the very first outpatient clinical trial of an AP system.
Landmark Approval: A milestone moment came in September 2016 when the
Fast-Tracked Designations: In spring 2019, the FDA granted its “breakthrough device designations” to four different closed loop technologies by Medtronic, Bigfoot Biomedical, and EoFlow. This designation was designed to help speed up the regulatory review process of innovative devices that the agency deems worthy.
AP Clinical Trials Abound
As it stands today, there are several hundred sites around the country and around the world conducting AP clinical trials, many of them in “outpatient” settings. This means study participants are not confined to a hospital or clinic. You can review many of the current studies online at ClinicalTrials.gov.
There’s No Such Thing as “Non-Invasive”
Lots of folks unfamiliar with diabetes are surprised to hear that all this equipment still pierces our skin, because they keep hearing about breakthrough “non-invasive” diabetes technology.
While it is true that inhalable insulin hit the market in recent years (MannKind’s Afrezza), so far that mealtime-only insulin has not been sufficient for use in an AP system. Current AP systems use a pump that delivers insulin through a small “subcutaneous” (under the skin) cannula.
It’s also been a dream for many decades to create a way to measure glucose without poking the skin, but we are not there yet either. So far, attempts to measure BG through the skin itself, through sweat, and even through the eyes have not been successful.
We at DiabetesMine have been covering AP development for as long as it’s been around. Here’s a selection of some of our articles over the years:
- Product Review: Tandem Diabetes Control–IQ (February 2020)
- Tandem Diabetes Control-IQ Tool Gets FDA Clearance! (December 2019)
- Diabetes Technology Review: New Do-It-Yourself Omnipod Loop (May 2019)
- An Artificial Pancreas Leader, on Her Life and Career with Type 1 Diabetes (April 2019)
- EoPancreas: A New Patch Pump Closed Loop System (March 2019)
- Diabeloop ‘Artificial Pancreas’ Approved in Europe (November 2018)
- Tidepool to Build an Official Artificial Pancreas Loop App! (October 2018)
- How Do-It-Yourself Diabetes Looping Works (April 2018)
- RileyLink: Homegrown Diabetes Closed Loop Technology (January 2017)
- FDA Approves First Pre-Artificial Pancreas in the Medtronic MiniMed 670G (September 2016)
- Meet Beta Bionics: New Business Structure for iLet Bionic Pancreas (April 2016)
- “My Time with iLet Bionic Pancreas” – First Human Trials! (March 2016)
- #WeAreNotWaiting Update – Slideset from the 2015 DiabetesMine Innovation Summit (November 2015)
- TypeZero Tech: More High Hopes for Closed Loop Commercialization (June 2015)
- Meet the Bigfoot Family and Their Homemade Closed Loop System (March 2015)
- With This Ring, I Close The Loop – and #OpenAPS (March 2015)
- Life on a Homemade Artificial Pancreas (December 2015)