For people with diabetes, keeping track of glucose levels is an important part of their day-to-day routine and usually involves a finger-prick blood test used with test strips. It’s a process, says Joel Goldsmith, senior director of digital devices at Abbott, that is “cumbersome and painful”.

But sensors that can automatically detect glucose levels without any need to draw blood are life-changing. One such device is Abbott’s FreeStyle Libre, which launched three years ago in Europe, and last year finally received FDA approval to launch in the US.

Freestyle Libre has two elements: the first is a disposable sensor, about the size of a £2 coin, that the user wears on the upper arm for 14 consecutive days or ten days in the US. The second is a radio-frequency identification (RFID) reader that – when held in close proximity to the sensor – displays a graph showing the user’s glucose levels for the past eight hours, and an indication of whether the levels are rising or falling. The reader stores 90 days’ worth of glucose data. There is also a version, FreeStyle Libre Pro, that is intended for health professionals.

Although there are some sensorbased devices already on the market, there are two things that make the Abbott device unique, says Goldsmith. One is the fact that it’s “effortless to scan the sensor and monitor the glucose”. The process of scanning and capturing the glucose level takes no more than a second. Some other sensor-based systems broadcast data continuously, but are perceived by some users, as “a little bit intrusive because it’s trying to get their attention at times when they may not want to be disturbed,” Goldsmith says. The FreeStyle Libre device, however, “requires the individual to take [a] limited amount of action, which gives people this sense that they are controlling the device, [and] not the other way around”.

The other benefit is that it provides contextual information about glucose levels. “It tells you where you’ve been, where you are and where you’re going,” Goldsmith says. It is also relatively cheap: in the UK, the reader costs about £60, as do the disposable sensors.

The device has been approved for use in the NHS by the National Institute for Health and Care Excellence (NICE). It is also possible to use a mobile app, rather than the proprietary reader.

Market outlook

The potential market for the FreeStyle Libre and other similar devices is huge: the US has six million people with either type 1 or 2 diabetes who require insulin to manage their glucose levels. There are now 450,000 people in 42 countries using Freestyle Libre, which has enabled Abbott to collect a large amount of data on how the devices are being used; 409 million glucose measurements from 64 million scans are carried out by more than 50,000 people in Europe. One of the findings is that people have been scanning their glucose levels 16 times a day – three times more than the minimum recommended in US and European guidelines. These findings have also been confirmed by clinical trials.

Every other sensor on the market today requires these calibration events, either two or four times a day, that essentially preserve the accuracy of the sensor.

The data also showed that the increased frequency of monitoring correlated with better glucose control. Average levels decreased, and there were sharp reductions in hypoglycaemia and hyperglycaemia. The amount of time that users’ glucose levels remained within the recommended range increased from 12 to nearly 17 hours a day.

So, how does it work? The device uses a proprietary technology called ‘wired enzyme’. “The sensor portion that is resident in the subcutaneous tissue is like a flexible fibre,” Goldsmith explains. “It’s technically made out of nylon and it’s coded with some chemistry, and that chemistry interacts with glucose molecules in the interstitial fluid. That interaction creates an electrochemical reaction.” The electrochemical signal, he adds, is then converted into a usable glucose value that is transmitted to the handheld device.

There were significant challenges involved in developing the Freestyle Libre device. The first, says Goldsmith, was factory calibration. “Our sensor maintains its accuracy profile without having to take confirmatory finger-stick measurements,” he says. “Every other sensor on the market today requires these calibration events, either two or four times a day, that essentially preserve the accuracy of the sensor. It recalibrates based on a blood glucose measurement. Our sensor, in contrast, never requires that, so when you’re using it, you can effectively go without using test strips at all. It maintains that accuracy profile for the full wear duration.”

The other difficulty, he adds, was developing a sensor that would remain on the body securely for 14 days. “That is not a trivial task, because skin cells are constantly falling off and being replaced, so when you have a foreign body stuck to the surface of the skin, over time, it’s going to lose its ability to remain securely attached, so that was another innovation in a fully disposable form factor,” he says. The sensor is water-resistant, so it can be worn during a shower or when swimming.

Data partnership

Last year, Abbott announced a partnership with medical start-up Bigfoot Biomedical to automate insulin delivery with Abbott’s sensor to measure glucose levels, in order to use this data to determine how much insulin the user needs. Bigfoot is planning two solutions, states Goldsmith. One is a pump-based insulin delivery solution “that uses the glucose information from the FreeStyle Libre sensor to inform how the insulin delivery should be automatically adjusted”. This has been specially designed to imitate the function of the pancreas.

The second solution has some similarities, but instead of using a pump as the insulin delivery method, it uses a new device known as a connected insulin pen. “It’s a more manually operated method of delivering the insulin, but with a Bluetooth chipset embedded in it, so it’s able to communicate dose information to a handheld device,” Goldsmith says. By using glucose level data from the sensor, the user can receive guidance on how much insulin to take and when to take it. Bigfoot is planning to announce a clinical trial in late 2018, and hopes to launch the product in 2020.

Goldsmith adds that the solutions being developed by Bigfoot are using advancements in machine learning, and the convergence between regulated medical devices and connected consumer electronic products, to help realise the potential of personalised medicine. It’s a big leap forward, he believes, but he sees the insulin pen as being especially beneficial. “While pumps have a place in that ecosystem, they’re not the solution for everyone, because they’re relatively expensive and it’s yet another device that you have to wear attached to your body, and not everyone wants to do that,” he explains. “I’m particularly keen on the solution that uses a connected insulin pen because it brings many of the known benefits of an automated insulin delivery system, but at a fraction of the cost.”

New players

The emergence of certain key technologies – smartphones, sensors and the internet of things – means there has been a spate of innovation in the field of diabetes management. Even in the past two or three years, the industry has seen a number of companies launch devices that represent a break with traditional approaches. In 2017, Medtronic Diabetes launched a system, similar to the one planned by Bigfoot, called the MiniMed 670G system for people with type 1 diabetes, which uses SmartGuard software to automate insulin delivery. The device includes a sensor to monitor glucose levels and delivers a variable rate of insulin throughout the day. Users will also be able to manually administer doses of insulin at meal times. However, this differs from Bigfoot’s system, which aims to deliver insulin automatically during meal times.

There is also the OneTouch Via, a wearable patch that delivers insulin on demand by pressing two buttons on the patch. InPen, which has been specially designed for users under 12, is a wireless-enabled insulin injector pen and associated smartphone app; the device tracks insulin doses automatically and sends data to the app via Bluetooth. The app helps patients calculate mealtime and correction doses, and can remind them when to take insulin.

Goldsmith believes it’s a particularly exciting time to be working in the management of diabetes because of the “tremendous amount of innovation” in a very short time span. There are three fundamental shifts that will make a significant change in the future, he argues. The first is the move “from discrete glucose monitoring using test strips to dense glucose data from bodyworn sensors. That’s a fundamental prerequisite, because the glucose data is a form of fuel for everything else.”

The second, he says, is “moving from proprietary handheld devices like the Freestyle Libre, which are purpose-built and operate in a disconnected state, to mobile medical apps running on connected consumer electronic products like smartphones and smartwatches; that creates a universal development platform for device manufacturers like us and a familiar user interface for millions, if not billions, of consumers. They also happen to be connected to the internet most of the time, so it creates a mechanism for routing that data to a series of other devices, apps or services.” The potential for using that data for either research or commercial purposes is enormous.

The final shift is “moving from isolated desktop software as a means of clinical decision support to distributed cloud computing, which is the home for all the advancements in machine learning,” he says. What cloud computing offers is the ability to handle analyse a mass of data and develop tailored treatments. Diabetes is uniquely placed to be at the forefront of these innovative shifts. “First and foremost, it’s a data-intensive disease; the devices that are used to manage and treat it are increasingly based on consumer electronic products – and it’s a growing global epidemic,” Goldsmith explains.

I’m particularly keen on the solution that uses a connected insulin pen, because it brings many of the known benefits of an automated insulin delivery system, but at a fraction of the cost.

Shift in focus

With diabetes, those three technological shifts come together to create a completely new approach to the management of disease. “You can easily imagine, over the next decade, that individuals are using devices to manage and treat diabetes,” Goldsmith states. “Those devices are effortlessly capturing information about themselves. So, whether that’s glucose, insulin, activity data, food consumption, stress or sleep, there’s a growing set of parameters that will be automatically captured by a set of devices. That data will be instantly and automatically uploaded to one or more cloud services that will then process it and apply advancements in machine learning, and deliver clinically proven treatment recommendations back down to that individual.”

Abbott is planning to take advantage of the shifts that Goldsmith has identified. It has already released two mobile medical apps and a cloud-based service. “We’re now building out that platform and enabling a whole ecosystem to emerge around it,” he highlights. “That’s part of the equation because no one company can do everything, so we are deliberately choosing to remain focused on the areas that we can be best in class, and then we will selectively partner with others to achieve [different] dimensions of diabetes management.”