D-glucose chain
D-glucose chain (source: Wikimedia Commons)

Imagine if your life suddenly depended on monitoring your body’s reaction every time you had a snack, skipped a meal, or ate a piece of candy. This is a reality for approximately 1.25 million people in the USA who have been diagnosed with Type 1 Diabetes (T1D).

People with T1D experience unhealthy fluctuations in blood glucose levels due to the destruction of beta cells in the pancreas by the person’s own immune system. Beta cells produce insulin, which is a hormone that allows your body to break down, use, or store glucose, while maintaining a healthy blood sugar level throughout the day. Presently, there is no cure for T1D, so patients must be constantly vigilant about maintaining their blood glucose levels within a healthy range in order to avoid potentially deadly consequences.

Currently, continuous glucose monitors (CGMs) are the most effective way to manage T1D. However, consumers have already become frustrated with the limitations of commercially available CGMs, and are developing at-home modifications to overcome them. This in turn, is influencing the direction of research and development in the biomedical devices industry, as multiple companies compete to create a CGM that appeals to the largest consumer population.

Thus, consumer-driven innovation in CGM data access, CGM-insulin pump integration, and glucose sensor lifespan has led to rapid growth in the field of diabetes management devices.

Coping with the highs and lows

Patients with T1D need to monitor their blood glucose levels to ensure they don’t become hyperglycemic(high blood glucose levels), or hypoglycemic (low blood glucose levels), both of which can cause life-threatening complications.

Throughout the late 1980s and 1990s, home glucose blood monitoring devices were the most accurate way to measure blood glucose levels. These devices use a lancet to prick the person’s finger to obtain real-time glucose levels from a drop of blood.

Although still used today by some diabetics as a primary means of T1D management, finger prick devices have considerable drawbacks. These include the physical pain that comes from frequent finger pricks, the static nature of the glucose reading, and the indiscretion and inconvenience of taking multiple readings throughout the day and night.

It is no wonder then that the market potential for a device that conveniently and accurately measures blood glucose levels continues to soar.

The continuous glucose monitor (CGM)

At the turn of the 21st century, the integration of technology and medicine introduced a novel way for patients to gain control of T1D. In 1999, MiniMed obtained approval from the U.S. Food and Drug Administration (FDA) for the first continuous glucose monitor (CGM). The device was implanted by a physician and recorded the patient’s glucose levels for three days. The patient then returned to the clinic to have the sensor removed and discuss any trends revealed by the CGM.

In 2001, MiniMed was acquired by Medtronic, a medical device company that specializes in making diabetes management devices. In 2003, Medtronic received FDA approval to launch the first, real-time, patient-use CGM device. This kick-started an ongoing competition to create more accurate, user-friendly CGMs from other diabetes management medical device companies, such as Dexcom Inc., Senseonics, and Abbott Laboratories.

Today, CGM devices consist of a thin, wire-like sensor that is inserted under the skin, which takes blood glucose readings every five minutes. These readings are sent wirelessly to an external transmitter and can be checked by the patient at the push of a button.

While most CGMs still need to be calibrated by using a finger prick device, they offer many advantages to blood glucose monitoring and diabetes management. CGMs not only give patients easy access to real-time blood glucose readings, but also track the readings over time so the patient can determine how quickly their blood glucose levels are increasing or decreasing. The CGM wearer can also customize their device with the healthy blood glucose range recommended by their endocrinologist. If the patient’s blood glucose levels rise above or fall below this range, the transmitter will alert the wearer to take action. “The CGM’s warning is a bit like the lane departure system in cars, but for your blood sugar,” says Dr. John Welsh, a medical writer at Dexcom, Inc., and a CGM user himself.

Consumer-driven innovation and competition

While medical devices are continuously being improved upon with the progression of technology and scientific knowledge, CGMs have recently been undergoing a rare, if not unprecedented bottom-up revolution.

Increasingly, tech-savvy consumers have realized the limitations of CGMs and are making at-home improvements to meet their needs, rather than waiting for new technology to become commercially available. This, in turn, is directing the future trajectory of research and development within companies as well as providing a rich environment for competition.

For example, John Costik, an engineer whose 4-year-old son was diagnosed with T1D in 2012, designed a simple phone app that allowed him to access the data from his son’s DexCom transmitter online so he could monitor his son’s glucose levels while he was at day care. He shared his innovation on Twitter and, unsurprisingly, discovered a large community of parents who had also been frustrated with the lack of access to their child’s blood glucose data.

Perhaps taking a cue from this, in 2015, Dexcom launched a “Share” feature for their devices, which allows CGM wearers to share their glucose information with up to five followers. In addition to family and friends, health care professionals can also follow their patients to assess how well the CGM wearer is managing their diabetes.

The DIY artificial pancreas

To relieve the mental burden of managing T1D, there has been a growing interest in “closed loop” artificial pancreas systems, which integrate CGMs with insulin pumps to automatically regulate insulin release. This would be especially useful at night, mitigating the need for patients to wake up and physically adjust their insulin pump if they were becoming hypoglycemic.

In 2013, Dana Lewis, a patient with T1D, and Scott Leibrand, a computer-networking engineer, created the Do-It-Yourself Pancreas System and founded the Open Source Artificial Pancreas System(OpenAPS). Rather than wait for the slow FDA approval of a new medical device, the OpenAPS community hopes to make artificial pancreas technology quickly available by engaging willing patients with T1D as innovators, independent researchers, and clinical trial subjects.

In direct response to this consumer-led movement, many major T1D medical device companies, including Dexcom, have a CGM-insulin pump integrated system in their pipelines. In 2016, Medtronic became the first company to receive approval for an artificial pancreas system. Their MiniMed 670G insulin pump communicates with the CGM to reduce insulin delivery at a predetermined hypoglycemic threshold.

While the system still relies on finger prick calibration, these devices will prove effective in T1D management and relieve a significant amount of anxiety for patients and their families. Increased patient compliance will also reduce the risk of developing co-morbidities that are caused by fluctuating blood glucose levels.

Meanwhile, the FDA keeps a close eye on amateur modifications to medical devices, which must go through rigorous trials to meet the FDA’s standards for safe and effective treatment of chronic conditions in humans. Since homemade modifications have not undergone these tests, the FDA prohibits the sale of these consumer-modified devices. However, the FDA is working with medical device companies to develop new, improved medical devices for diabetes and get them to market as quickly as possible without compromising consumer health and safety.

Extending the lifespan of the CGM sensor

CGM wearers have also noted the short lifespan of the sensors. The requirement to replace the sensor every 7-14 days is inconvenient and costs money. Because of this, some patients have confessed to wearing a sensor beyond its expiration date. This can be dangerous for the patient, as the sensor’s performance may decline beyond its period of intended use and thus affect the accuracy of CGM readings.

Senseonics has seized this market opportunity and developed Eversense, an implantable sensor that lasts up to 90 days and would completely replace finger prick tests. As opposed to Dexcom’s and Medtronic’s at-home sensor replacement systems, the Eversense sensor must be implanted by a minor surgical procedure conducted at a doctor’s office. The Eversense transmitter also vibrates directly on the skin if the patient’s blood glucose level falls out of the healthy range, eliminating the need to carry a mobile device to receive alerts.

Eversense is currently under evaluation by the FDA for premarket approval. However, Eversense has already gained the CE Mark approval, allowing the company to start marketing the device in Europe. In 2016, Senseonics partnered with Roche, giving the big pharmaceutical company exclusive rights to market Eversense abroad. In addition, Roche and the venture firm New Enterprise Associates are the top two shareholders in Senseonics, providing major financial and marketing support if Eversense is approved in the U.S.

Tackling the cost of CGMs

Another large obstacle for consumers is the cost of the CGMs. CGMs are more expensive than finger prick monitors and the price can also vary depending on the CGM’s components and the company that produces them. Sensors typically cost between $35-$100, whereas transmitters can cost upwards of $1,000. Furthermore, the out-of-pocket cost varies greatly depending on an individual’s insurance provider. As of March 2017, Dexcom’s G5 Mobile CGM is the only FDA approved system that meets all of the criteria to be covered by Medicare.

“Retrospective” or “professional” CGMs provide a way to alleviate the financial burden of CGMs on consumers. Patients with a retrospective CGM only need to purchase the sensor component of the CGM, which can often be covered by insurance. Meanwhile, a professional clinic buys the corresponding transmitter. This approach allows the same transmitter to be used to scan the sensors of hundreds of patients, saving money for both the insurance companies and the consumers.

Abbott Laboratories has created a retrospective CGM called the Freestyle Libre Pro, which was approved by the FDA in 2016. A doctor inserts a transcutaneous glucose sensor, which records readings over a time period of up to two weeks. The patient then returns to the clinic where the sensor is removed and scanned to obtain the stored glucose readings. These readings provide health care professionals a comprehensive review of a patient’s blood sugar levels over time and how well they are managing their diabetes.

Abbott has also worked to alleviate the physical toll of T1D management by “factory calibrating” their devices, eliminating the need for painful finger pricks. In September 2017, Abbott’s Freestyle Libre Flash, became the first FDA approved, real-time CGM that does not require finger prick calibration. Many consumers, especially those that still rely on finger prick tests as the main method of diabetes management, are ready to embrace this new technology.

Importantly, neither the Libre Pro nor the Libre Flash has the capability to alert the wearer if their blood glucose readings fall outside of the normal range. However, the affordability of Abbott’s devices appeals to an important market niche. Additionally, Abbott focuses heavily on marketing their CGMs toward patients with Type II Diabetes (T2D) who may currently rely solely on clinical management or finger prick tests to manage their diabetes.

Creating the ultimate CGM

As established companies work to improve and refine their CGM systems, new competitors are still emerging in the field.

GlySens, a privately owned biomedical technology company in San Diego, California, is developing a CGM system called Eclipse ICGM that will be designed to overcome multiple limitations of current CGM monitors in one device.

The ICGM system will be designed to last up to one year, meaning there will be no components that need to be changed or charged every few days. This will result in fewer visits to the doctor. It will also be completely subcutaneous, making it very discreet. This system promises to do away with using finger prick glucose monitoring entirely.

Currently, GlySens is conducting a clinical trial to assess the safety and tolerance of their long-term implanted glucose-monitoring sensor in humans.

Type II diabetes provides a growing market potential for CGMs

Although current CGMs are primarily targeted toward people with T1D, these patients only make up about 5% of the diabetic population in the USA. The remaining 95% of diabetics (29 million people) have T2D, which occurs when a person’s cells are unable to effectively use insulin.

Moreover, approximately one-third of Americans adults (86 million) are living with pre-diabetes. It is predicted that T2D will continue to remain a major health concern in the future, with some projections predicting the prevalence to rise over 50% by 2030.

Unlike T1D, T2D is usually diagnosed well into adulthood and a physician’s recommendation to start glucose monitoring can represent a sudden and challenging lifestyle change. Therefore, convenience and cost of CGMs will be a huge factor in whether companies can successfully market these devices to the T2D population.

CGMs would allow patients to share their glucose level readings with doctors to analyze data trends so they can develop a T2D management plan. Interestingly, research from Dr. Jeremy Pettus’s lab at the University of California, San Diego, suggests that the ability to share CGM data with friends, family, and health care professionals may provide motivation for T2D patients to maintain a healthier lifestyle.

Thus, a successful marketing strategy toward T2D patients could substantially increase the consumer base for any company involved in diabetes management.

A bright future for CGMs

Before the advent of CGMs, T1D was very stressful for the patient and their loved ones. CGMs alleviate some of this burden by providing data trends in addition to a static blood glucose reading, which allows patients with T1D to manage their diabetes more effectively.

CGMs are a prime example of how technology and science can be integrated to improve the lives of patients with chronic conditions like T1D. CGMs are also unique in the way consumers have taken it upon themselves to create modifications to these medical devices, a space that was previously reserved for research and development branches of biotechnology companies.

With multiple competitors vying to meet the needs of an increasingly technologically literate consumer base, and with an ever-expanding market, it will be exciting to monitor the future development CGMs.

Article image: D-glucose chain (source: Wikimedia Commons).