continuous glucose monitor (CGM)

The Artificial Pancreas: What Is It and When’s It Coming?

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You’ve probably heard about the artificial pancreas, but are you up to speed on what’s happening in this rapidly evolving field?

First of All, What Is It Really?

The artificial pancreas (AP) is a device that mimics the blood sugar function of a healthy pancreas. It has three parts: a sensor for continuous glucose monitoring, a pump to deliver insulin, and a laptop or cell-phone component that directs the pump to deliver insulin as needed.

Most systems will deliver insulin alone, but some will be able to deliver both insulin and glucagon*.

How It’s Different from CGM

Artificial pancreas systems are often called “closed-loop” because they talk to both the sensor and the pump, bridging the gap between the two. The goal is to make a continuous loop without the need for human intervention. In testing so far, AP systems have often resulted in more time in target glucose ranges with less hypoglycemia, and they have also shined in controlling blood sugars overnight. They are not a cure by any means, but they are a huge improvement and will allow for diabetes management to go a little more on autopilot in the near future.

50 Years in the Making

The first precursors of the artificial pancreas date back to the 1970s. In the 50 years since, improvements have been made on all fronts: control algorithms are getting more predictive and less reactive, and pumps and glucose sensors are getting more accurate. Yet many challenges remain, such as the need for faster insulin, more stable glucagon, and systems that can work without user intervention, e.g., during meals and exercise.

The Future Is Almost Here

In June of 2017, Medtronic launched the first commercialized product, Minimed 670G.

The Medtronic device is a “hybrid” system due to the need to manually interact for meals and exercise. Hailed as a major advance towards a fully-automated artificial pancreas system, the 670G will be followed by other closed-loop systems in the coming months and years, with more and more academic group and industry collaborations being announced.

MiniMed 670G

One such effort – the IDCL (International Diabetes Closed Loop) Trial – is another example of the degree of collaboration between academic centers and industry. Led by the University of Virginia in conjunction with centers in Europe, companies like TypeZero Technologies, Tandem Diabetes Care, Dexcom and Roche Diagnostics are also involved. Other companies like Insulet (Omnipod) and Bigfoot are developing AP systems as well.

If You Just Can’t Wait

Alongside conventional development of AP systems, “Do It Yourself” or DIY movements spearheaded by patient and engineering communities are gaining visibility with a reported 400+ PWD currently using DIY artificial pancreas systems. Initiatives such as DIYPS.org and #wearenotwaiting are providing information on the internet to help people with diabetes build their own AP systems using commercially available CGM and pumps while providing information on how to set up control algorithms.

These systems require a great deal of user learning and commitment. While probably not for everyone and regulatory authorities sending out caveats on the potential risks involved, they can be a way for people to access artificial pancreas technology now before other systems are cleared for use.

At the 2017 Taking Control Of Your Diabetes Conference & Health Fair in San Diego, there was a panel discussion with five people who experimented with DIY systems and shared their thoughts, advice, and personal experiences.  You can watch the seminar and hear what they had to say here.

As a result, we can expect several artificial pancreas options in the coming years, which is amazing news! Systems will differ, but the goal will be the same: to reduce the burden of living with diabetes until a cure is found. We look forward to seeing more and more options in this space, and send kudos to all involved for their perseverance, passion, and commitment!

*Glucagon causes the liver to release stored glucose, raising blood sugar levels. It can be used to treat severe hypoglycemia.

Libre vs. Dexcom: A Diabetes Educator’s Experience

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Libre vs. Dexcom

When I heard the news that the Freestyle Libre was coming to the U.S., I was so excited, especially since it adds to the options for self-management technology for people with both type 1 and type 2 diabetes.

So, last week, I took advantage of the free Freestyle Libre reader and sensor offer for current Dexcom users.

I was so excited to try out the Libre and wear it with the Dexcom G5 to compare the two as a self-management experiment. I was prepared for the two devices to differ as one is a continuous glucose monitor (Dexcom) and the other is a flash glucose monitor (Libre). Here are my thoughts.

Ten Thoughts of a Certified Diabetes Educator

1. Filling the Prescription: Win for the Libre

I was able to get my hands on a Libre within 36 hours of claiming the offer. I contacted my endocrinologist to write me a prescription and almost immediately Walgreens worked on obtaining a Libre system for me. My Walgreens didn’t have the Libre in stock, so they placed an order, and I was able to pick it up the next day. Whenever I try to re-order Dexcom supplies through my third party distributor, it seems to be disastrous, and it takes a week or so to receive my shipment.

Considerations: If you do not have insurance coverage for a CGM, have a high deductible, or cannot afford your out-of-pocket cost with coinsurance, the Libre is a much more affordable option. However, make sure that your insurance will cover the Libre. If insurance covers the Dexcom (and you have good insurance coverage), but not the Libre, then Dexcom may be a more affordable option.

2. Insertion Process: Win for the Libre

The insertion instructions for the Libre are understandable and easy to follow which differs from the difficult Dexcom insertion process.

Considerations: If you are unfamiliar with diabetes technology, have low dexterity or have vision problems, the insertion process for the Libre may be much smoother than insertion of the Dexcom.

3. Sensor Life: Win for the Dexcom

The Libre sensor lasts ten days, and the Dexcom sensor lasts only seven days. However, many people have discovered how to trick the Dexcom sensor into continuing for much longer than seven days. The Libre is too smart to be fooled and requires a new sensor after ten days.

4. Sensor Start-Up: Win for the Dexcom

The Libre takes 12 hours to warm-up. I put it on before bed, but I still had to wait a few hours to use it when I woke up. I was anxious to get started! The two-hour start-up for the Dexcom isn’t so bad after all.

5. Calibration: Win for the Libre

The Libre is factory calibrated, so it does not need to be calibrated after warm up or throughout its ten-day session. The Dexcom requires two calibrations after its two-hour warm up and then one calibration every 12 hours.

At first, I thought this was an absolute win for the Libre. However, I noticed that there were a few instances where my Libre was significantly (60+ numbers off) from my meter reading and Dexcom reading. I understand that the Dexcom will be closer to the meter reading since it uses the meter reading for calibration but I felt scared that I couldn’t tell the Libre it was wrong to re-adjust it. I don’t think I’m fully ready to trust factory calibration yet.

Considerations: The factory calibration is a beautiful feature as it reduces user-burden. All the user has to do is insert the Libre before starting the session. This feature is beneficial for those who cannot or will not check their blood glucose manually throughout the day.

6. Graphs: Win for the Dexcom

The Libre gives a similar graph as the Dexcom. Both graphs showed comparable glucose variability patterns even if the numbers differed slightly. The Libre reader device reports and the Dexcom clarity reports have similar information.

The trend arrows are to be used similarly on both devices. However, my Dexcom seemed to be much more accurate with arrows when I was dropping. I self-manage based on my Dexcom trend arrows, so this was concerning to me.

One benefit of the Libre though is that it does not seem to lose signal like the Dexcom does, leaving lapses of glucose data in the graph.

Considerations: The Libre is still an excellent tool to look at average daily glucose patterns and make adjustments with your healthcare provider.

7. Accuracy: Win for the Dexcom

The Libre was significantly off from my Freestyle meter which is built into the Omnipod PDM, but the Dexcom matched up pretty closely due to calibration from the meter reading. However, since the FDA approved the G5 to dose off, I think it is safer to use the Dexcom reading for treatment decisions.

Considerations: My personal experience may differ from others. Additionally, research has found that the Libre’s mean average relative distance (MARD) is less than the Dexcom G4’s MARD—meaning that the Libre is more accurate than the Dexcom G4. There is limited research on the G5 MARD vs. the Libre though. If you just want a device to look at glucose trends and not to dose off of, there is no problem with the Libre (from my personal experience).

8. Reading Blood Glucose: Win for the Dexcom

The Libre requires that the user presses a button on the reader device to see their current blood glucose reading. Though I thought it would be annoying to carry around the reader device, it did not bother me!

dexcom integration

However, I do depend on looking at my blood glucose and trends throughout the day on my Apple Watch (through the Dexcom app) when I am at work, so having to pull out the device to check my blood glucose was much more apparent to my co-workers. The Libre doesn’t (currently) have any mobile apps with sharing features in the U.S. I also depend on the sharing feature for safety. Now that I have used a CGM with alerts and continuous glucose data for the past four years, missing continuous data makes me anxious.

Considerations: If you self-manage fine by checking your glucose a few times per day, the Libre may be less annoying and work very well for your needs.

9. Alarms: Win for the Dexcom

The Libre has no alarms like the Dexcom. I am not hypo-unaware (as of now), but I still worry about not waking up for a low blood sugar overnight. The alarms provide a safety net.

Considerations: If you are hypo-unaware or live alone, it may be safer to consider a device with alarms. Additionally, it appears there is a company (BluCon by Ambrosia) that does make an add-on device for the Libre so that you can receive alerts continuously and overnight for lows and on a mobile application.

10. Adhesive: Tie

I cleaned off my site area with alcohol before inserting the Libre. I was unsure of the guidelines for using skintac, so I did not use any before insertion.

After two days the Libre began to peel off, and I had to reinforce it with Tegaderm. The Dexcom also does not have great adhesive.

However, I have been using the Dexcom long enough to figure out the best way to make it stick for me (donut-shaped application of liquid skintac before insertion, gifgrips on after insertion, followed by additional liquid skintac on top).

Considerations: Both the Libre and the Dexcom seem to cause allergic reactions in some.

Final Thoughts

Trialing the Libre was an awesome opportunity as it gave me a sense of having patient choice for self-management tools.

However, I am not sure I am mentally ready to use the Libre over the Dexcom. I am used to using my Dexcom G5 CGM and have become somewhat dependent on its benefits for my peace of mind and sense of safety.

There are still many clear clinical benefits to using the Libre, however, and the best fit depends on individual self-management needs.

Automated Insulin Delivery (Artificial Pancreas, Closed Loop)

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artifiical pancreas

 

The development of automated insulin delivery has many names – artificial pancreas, hybrid closed loop, Bionic Pancreas, predictive low glucose suspend – but all share the same goal: using continuous glucose monitors (CGMs) and smart algorithms that decide how much insulin to deliver via pump. The goal of these products is to reduce/eliminate hypoglycemia, improve time-in-range, and reduce hyperglycemia – especially overnight.

See below for an overview of the automated insulin delivery field, focused on companies working to get products approved. Do-it-yourself automated insulin delivery systems like OpenAPS and Loop are not included here, though they are currently available and used by a growing number of motivated, curious users.

We’ve also included helpful links to articles on specific product and research updates, as well as some key questions.

Who is Closing the Loop and How Fast Are They Moving?

Below we include a list of organizations working to bring automated insulin delivery products to market – this includes their most recently announced public plans for pivotal studies, FDA submissions, and commercial launch. The organizations are ordered from shortest to longest time to a pivotal study, though these are subject to change. This list excludes those without a commercial path to market (e.g., academic groups). The first table focuses on the US, with European-only systems listed in the second table.

Updated: November 4, 2017

US Products

Company / Organization Product Latest Timing in the US
Medtronic MiniMed 670G/Guardian Sensor 3 – hybrid closed loop that automates basal insulin delivery (still requires meal boluses) FDA-approved and currently launching this fall to ~35,000 Priority Access Program participants in the US. Pump shipments to non-Priority Access customers will start in October, with sensors and transmitters to ship by the end of 2017 or early 2018. Medtronic is experiencing a global CGM sensor shortage that won’t resolve until spring 2018.
Tandem t:slim X2 pump with built-in predictive low glucose suspend (PLGS) algorithm; Dexcom G5 CGM

t:slim X2 pump with built-in Hypoglycemia-Hyperglycemia Minimizer algorithm; Dexcom G6 CGM (including automatic correction boluses)

 Launch expected in summer 2018. Pivotal trial now underway, with FDA submission expected in early 2018.

Launch expected in the first half of 2019. Pivotal trial to begin in the first half of 2018.
Insulet OmniPod Horizon: pod with built-in Bluetooth and embedded hybrid closed loop algorithm, Dash touchscreen handheld, and Dexcom G6 CGM

User will remain in closed loop even when Dash handheld is out of range

 Launch by end of 2019 or early 2020, with a pivotal study in 2018
Bigfoot Biomedical Smartphone app, insulin pump (acquired from Asante), and a next-gen version of Abbott’s FreeStyle Libre CGM sensor (continuous communication)

The smartphone is expected to serve as the window to the system and complete user interface

 Launch possible in 2020, with a pivotal trial expected in 2018
Beta Bionics Bionic Pancreas iLet device: dual chambered pump with built-in algorithm; hybrid or fully closed loop; insulin-only or insulin+glucagon; custom infusion set, Dexcom CGM

Likely to launch as insulin-only product, with glucagon to be optionally added later

Currently using Zealand’s pumpable glucagon analog

 Insulin-only: possible US launch in the first half of 2020, with a pivotal trial to start in the beginning of 2019.

Insulin+glucagon (bihormonal) pivotal trial expected to start in the beginning of 2019. Timing of FDA submission and launch depend on a stable glucagon, among other things.

European Products

Company / Organization Product Latest Timing in Europe
Medtronic MiniMed 640G/Enlite Enhanced – predictive low glucose management

MiniMed 670G/Guardian Sensor 3 – hybrid closed loop that automates basal insulin delivery (still requires meal boluses)

 Currently available in Europe

No timing recently shared. Approval was previously expected in summer 2017
Diabeloop Diabeloop algorithm running on a wireless handheld, Cellnovo patch pump, Dexcom CGM Pivotal trial expected to complete in February/March 2018. Possible European launch in 2018
Roche, Sensonics, TypeZero Will use Senseonics’ 180-day CGM sensor, Roche pump and TypeZero algorithm Pivotal trial expected to begin in Europe in early 2018
Cellnovo, TypeZero Cellnovo patch pump with integrated TypeZero algorithm; presumably a Dexcom CGM Aims for a 2018 European launch. No pivotal trial details shared

Helpful Links

Medtronic: MiniMed 670G

Tandem

Insulet

Bigfoot

Beta Bionics

Test Drives:

test drive – UVA’s Overnight Closed-Loop Makes for Great Dreams. Kelly participates in UVA’s overnight closed loop trial and reports back on an incredible opportunity for the field to move fast, reduce anxiety, and beat timelines.

test drive – Kelly and Adam take UVA’s DiAs artificial pancreas system home 24/7 for a three-month study. Their key takeaways, surprises, and next steps.

Key Questions for the Artificial Pancreas

Are patient expectations too high? If we expect too much out of first-generation artificial pancreas systems – e.g., “I don’t have to do anything to get a 6.5% A1c with no hypoglycemia” – we might be disappointed. Like any new product, early versions of the artificial pancreas are going to have their glitches and shortcomings. Undoubtedly, things will improve markedly over time as algorithms advance, devices get more accurate and smaller, insulin gets faster, infusion sets improve, and we all get more experience with automated insulin delivery. But it takes patience and persistence to weather the early generations to get to the truly breakthrough products. We would not have today’s small insulin pumps without the first backpack-sized insulin pump; we would not have today’s CGM without the Dexcom STS, Medtronic Gold, and GlucoWatch; we would not be walking around with smartphones were it not for the first brick-sized cellphones. Our research trial experience with automated insulin delivery recalibrated our expectations a bit – these systems are going to be an absolutely terrific advance for many patients, but they will not replace everything out of the gate. Let’s all remember that devices need to walk first, then run, and it’s okay if the first systems are more conservative from a safety perspective.

What fraction of patients will be willing to wear some type of automated insulin delivery system? Right now, many estimate that ~30% of US type 1’s wear a pump, and about 15% to 20% wear CGM. There are a lot of reasons why that may be the case, including cost, hassle, no perceived benefit, no desire to switch from current therapy, wearing a device on the body, alarm fatigue, etc. Will automated insulin delivery address enough of these challenges to expand the market?

Will healthcare providers embrace automated insulin delivery? Today, healthcare providers lose money when they prescribe pumps and CGM – they are very time consuming to train, prescribe, and obtain reimbursement for. We need to make sure that automated insulin delivery systems make providers’ lives easier, not more complicated.

Will there be a thriving commercial environment and reimbursement? It’s extremely expensive to develop and test closed-loop systems, and companies will only develop them if there is a commercial environment that supports a reasonable business. Reimbursement is a major part of that, and it’s hard to know if insurance companies will pay for closed-loop systems for a wide population of patients. We are optimistic that reimbursement will be there, especially if systems can simultaneously lower A1c, reduce hypoglycemia, and improve time-in-range.

What’s the right balance between automation and human manual input? The holy grail is a fully-automated, reactive closed loop that requires no meal or exercise input. But insulin needs to get faster to make that a reality. For now, daytime systems need to deal with balancing human input with automation, and there’s an associated patient learning curve. How much should automated insulin delivery systems ask patients to do? How do we ensure patients do not forget how to manage their diabetes (“de-skilling”) as systems grow in their automation abilities?

Insulin-only or insulin+glucagon? Ultimately, we believe that the question is partially one of patient preferences. There will be some patients who may want the extra glycemic control offered by the dual-hormone approach and will be willing to accept a bit more risk or a more aggressive algorithm. An insulin+glucagon system could be helpful for those with hypoglycemia unawareness, and if such a system makes it to the market, some patients will certainly want to give it a try. We believe a range of options is a good thing for people with diabetes, since all systems and products have pros and cons. Ultimately, cost considerations may present the largest factor in adoption. An insulin+glucagon system certainly brings multiple cost elements to consider – a second hormone, a dual-chambered pump, custom infusion sets, potentially higher training, etc. It’s hard to know at this point how the relative costs/benefits will exactly compare to insulin-only systems.

A 180-Day CGM: Senseonics’ Eversense XL Approved in Europe

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Eversense CGM for diabetes

 

Implanted sensor with on-body transmitter lasts more than 12x longer than other CGMs; launch expected in Europe in late 2017

Senseonics’ Eversense XL continuous glucose monitoring (CGM) system, featuring an implanted sensor with extended life of up to 180 days, has been approved in Europe. This decision doubles the previously-approved 90-day wear time, meaning that the sensor can be used more than 12 times longer than any other CGM sensor available in Europe.

Senseonics plans to launch Eversense XL in Europe later this year. In the US, the 90-day version remains under FDA review, with a possible approval later this year or in early 2018.

Like the 90-day Eversense CGM system, the 180-day Eversense XL features a small sensor (~5/8 inches long and ~1/8 inch in diameter; slightly larger than a pill) that is implanted in the upper arm. The 5-10 minute procedure can be carried out in a typical doctor’s office. It requires only local anesthesia and involves a small incision about one-quarter inch (5 to 8 mm) long. The user then wears a rechargeable transmitter device on the skin directly above the implanted sensor. The transmitter, which can be taken off and put back on at any time, powers the sensor and sends real-time glucose readings and trends to a smartphone.

Both the smartphone and on-body transmitter can alert the user of high or low glucose levels. When the phone is out of range, the on-body transmitter itself can provide a vibration alert – a cool feature that also distinguishes Eversense from other CGMs.

Eversense still requires two fingerstick calibrations per day and is not approved for insulin dosing or as a replacement for fingersticks (like Dexcom’s G5 or Abbott’s FreeStyle Libre).

Thus far, Senseonics has slowly rolled out Eversense in Europe, and we’ll be interested to see if the launch broadens and this new 180-day CGM option gains traction. Interestingly, approximately 80% of those who have gone on Eversense in Europe previously wore CGM.