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, well-meaning family and friends may even be asking if you have one of these yet. Make no mistake: this is a teaching moment for everyone involved.


{Editor's Note: This is mainly a primer for the uninitiated, but also a useful overview for anyone effected by diabetes.}


What Is an ‘Artificial Pancreas’ to Begin With?

Although ‘Artificial Pancreas’ 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 get to the point where they can connect various diabetes devices, using a combination of cables and wireless technology, to create a system that can mimic what a healthy pancreas does, by monitoring glucose levels and delivering insulin as needed.

So right now, a so-called ‘Artificial Pancreas’ is essentially an insulin pump connected to a continuous glucose monitor (CGM), controlled via some kind of receiver (usually a smartphone) using sophisticated software algorithms to make the whole thing work.

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The idea is to automate blood glucose control as much as possible, so the wearer no longer has to take fingerstick blood sugar readings, and then do complex math to determine how much insulin to dose, or how much to reduce insulin delivery based on low 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 still being studied, and as of this writing (April 2016), there is no commercial AP product on the market yet. But incredible strides are being made, and new groups seem to be emerging all the time to work on this exciting advancement.

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 continuous glucose monitor (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 CGMs on the market in the U.S., from Dexcom and Medtronic
  • a controller (usually an iPhone) 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
  • sometimes glucagon, a hormone that rapidly increases blood glucose, used here as an antidote to hypoglycemia (low blood sugar)

 

Who’s Creating These AP Systems?

Here’s a list of companies involved in developing a market-ready AP system, in alphabetical order:

Beta Bionics - Born out of the University of Boston iLet Bionic Pancreas Project more than a decade, Dr. Ed Damiano and team have been working on this for more than a decade -- animal trials happened in 2005 and human trials began in 2008, and it's evolved in the years since. The "Go Bionic" team in 2016 formed a commercial, public benefit corporation to develop and bring their iLet system to market. This dual-chambered device will have one of the most sophisticated user interfaces, and will include pre-filled cartridges of insulin and glucagon to eliminate the need for manual filling by the user.

Bigfoot Biomedical - Established in 2014 by former JDRF CEO Jeffrey Brewer, Bigfoot has hired some of the most prominent AP entrepreneurs and even purchased the IP (intellectual property) and Milpitas, CA, office space from now-defunct insulin pump company Asante Solutions. They have since teamed up with Abbott Diabetes Care to use a next-generation FreeStyle Libre Flash monitoring system with the device, and Bigfoot's also acquired Timesulin to create a smart pen version of their automated insulin delivery system. You can read the origin story here.

CellNovo & Diabeloop - a European pump company and French research consortium developing and testing new AP systems in the UK and France.

Dexcom - the leading CGM sensor technology from this San Diego-based company is at the heart of a large majority of AP systems under development, including some DIY (do-it-yourself) 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 model will be used in closed loop systems coming down the road with Tandem's t:slim X2, Insulet's OmniPod Horizon, and more.

Dose Safety - a Seattle-based startup developing a sophisticated controller for use in AP systems.

DreaMed Diabetes - an Israel-based startup established in 2014 as a spin-off the DREAM International Consortium, in order to commercialize the Artificial Pancreas technology behind its Glucositter software. In 2015, Medtronic signed an agreement to use that Glucositter in its future closed loop technology.

Insulet Corp. and Mode ACG - the Boston-based manufacturers of the tubeless OmniPod insulin pump announced integration with the Dexcom CGM in 2014, and recently struck a deal with AP software firm Mode AGC (Automated Glucose Control LLC) to develop and incorporate their advanced AP algorithm in the system.   

Medtronic Diabetes - the insulin pump market leader and only company that manufacturers 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 artificial pancreas software Glucositter in its future systems.

On Sept. 28, 2016, Medtronic’s Minimed 670G “hybrid closed looop” system was approved by the FDA -- becoming the first-ever approved system to automatically dose insulin based on CGM readings. It is therefore the first "pre Artificial Pancreas" 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. The product is the first of its kind worldwide, and future generations will make the MedT systems more automated.

Pancreum - 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 - makers of the innovative iPhone-ish t:slim insulin pump are developing an integrated pump-CGM system featuring both the predictive hypoglycemia algorithm and a predictive hyperglycemia (high blood sugar) algorithm. Tandem received FDA approval for its basal-only adjusting "Basal-IQ" tech in 2018 that automatically shuts off insulin when a hypo is predicted, and by mid-2019 the company expects its automatic bolus-for-highs version, Bolus-IQ, to be available. They're working with Type Zero Technologies for future closed loop capabilities.

TypeZero Technologies - A Charlottesville, VA-based startup that spun off from years of closed loop research and development of an AP system at the University of Virginia (UVA). They are working to commercialize what the UVA originally called DiAs (short for Diabetes Assistant system), and this will be integrated with the Tandem Diabetes closed loop technology.

Artificial Pancreas Lingo

Here’s the skinny on some of the key terminology involved:

Algorithms - in case you’re unfamiliar, 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 actually, 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 - per definition, 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 Artificial Pancreas, where insulin delivery is regulated by feedback from an algorithm based on CGM data.

Dual Hormone - this refers to AP systems that contain both insulin and glucagon, the hormone that has the opposite effect on blood sugar levels.

UI (user interface) - a technology term that refers to everything designed into a device with which a human being may interact -- the display screen, colors, buttons, lights, icon characters, help messages, etc. Researchers have come to realize that a poorly designed UI could be the deal-breaker that could keep 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 - that feature allowing 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.

#WeAreNotWaiting - the hashtag that 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 - a homemade “do-it-yourself” Artificial Pancreas system 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.    

 

Some Important Things to Know About AP Systems

Here are some important facts about AP development, in no particular order:

 

FDA and JDRF are Pushing Hard on AP Progress

Actually, they’ve been pushing on this for a full decade!

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 AP technology as one of its “Critical Path” initiatives to drive innovation in scientific processes.

Guidance: Then 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 FDA approved the Medtronic Minimed 670G, a "hybrid closed loop" system that automatically adjusts basal insulin and can predict some hypo and hyperglycemia. This device partially closes the loop but is not a full AP that does everything for the user. This was the result of more than a decade's work on advocacy, policy, research and product development. This regulatory approval is expected to pave the way for other closed loop systems to follow.

 

Clinical Trials for Artificial Pancreas 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, meaning study participants are not confined to a hospital or clinic.

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Read All About It: Ongoing Coverage of Artificial Pancreas Progress

We at the ‘Mine 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:

NEWSFLASH: FDA Approves First Pre-Artificial Pancreas in the Medtronic Minimed 670G (Sept. 29, 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)

Pancreum Progress Report: Wearable Closed-Loop System Now a Prototype (August 2014)