Non-Invasive Glucose Monitoring: Hope or Hype?

This content originally appeared on diaTribe. Republished with permission.

By Andrew Briskin

For years, people with diabetes have sought out an accurate way to measure glucose without the need for fingersticks or fluid samples. Here’s a look at the latest in research and development of non-invasive glucose monitoring devices.

Over the last two decades, dozens of companies worldwide have sought to develop a non-invasive glucose monitor – a sensor that could measure your glucose levels without puncturing the skin or having to insert a device into the body.

The majority of these devices so far have either failed to work or have not received FDA approval. However, researchers have been persistent, and in recent years, have fine-tuned different forms of non-invasive monitoring technologies, offering promise that a device may eventually reach the market.

“There is significant demand for a non-invasive glucose monitor, as most of our patients hate sticking their fingers multiple times each day to check their blood sugars,” said Dr. Farah Khan, an endocrinologist and Clinical Assistant Professor of Medicine at the University of Washington. “If a non-invasive monitor could somehow be [as accurate as] CGMs currently available, this would be a huge step forward.”

These sensors could make fingersticks and the need to insert a continuous glucose monitor (CGM) a thing of the past. Some other advantages include avoiding the pain of a needle, eliminating false readings due to contamination by substances on the surface of your hands, and limiting waste from disposable testing supplies such as test strips or lancets.

Additionally, some non-invasive monitors have no disposable components, which could wipe out recurring costs for testing supplies, only requiring a one-time purchase.

Optical technology in the pipeline

The discussion around monitoring glucose levels without the need for blood or other bodily fluids is not new. In fact, devices have attempted to use various forms of optical technology since the 1990s.

Optical technology refers to any method that can identify different substances in a fluid (like blood) based on the interaction of those substances with electromagnetic radiation or light.

Nearly all of the non-invasive glucose monitors currently in development use some form of optical technology to collect glucose measurements.Physicians and scientists have already used optical techniques in many areas outside of diabetes. For example, X-ray machines can create images of broken bones based on how our bones absorb and reflect X-rays differently than the surrounding bodily tissue. Nearly all of the non-invasive glucose monitors currently in development use some form of optical technology to collect glucose measurements.

While different devices use different types of light (some use infrared waves, others radio frequency waves), the basic principle is the same. A monitor shines a beam of light through your skin, which is then reflected and scattered by the glucose in your blood. The sensor then detects signals from the light that is reflected back. Glucose exhibits a unique reflection pattern that differs from the other components of blood; the difference in signals is how the sensor determines your glucose level.

Of course, this is much easier said than done. One of the key challenges to developing a non-invasive glucose monitor has been determining the differences between glucose and the other components in our blood.

“The glucose signal from an optical sensor is small, and other molecules in the body produce interfering signals that are similar, which is called noise,” said Dr. David Klonoff, Medical Director of the Diabetes Research Institute in San Mateo, California, and editor-in-chief of the Journal of Diabetes Science and Technology. “The ratio of glucose signal to noise is often very small and it can be difficult to isolate the glucose signal itself.”

However, our ability to isolate glucose signals alone has improved.

“Newly-developed artificial intelligence and machine learning algorithms have given us greater computational power to isolate a glucose signal from the noise,” said Klonoff. “We are getting closer to seeing a commercially viable product emerge, thanks to improved sensors that are smaller and more accurate.”

There are varying degrees of optimism as to when this technology might become accurate enough to be used in an FDA-approved glucose monitor.

“The FDA has never cleared an optical non-invasive glucose monitor,” said Klonoff. “However, I expect that the regulatory requirements for eventual clearance will be different than what is required for currently cleared products that measure glucose in the blood or interstitial fluid.”

Somewhat less optimistically, Khan said she worries that these forms of optical technology may not have enough precision or accuracy to help our patients manage their diabetes.

Other non-invasive technology in the works

Outside of non-invasive optical glucose monitors, several companies have sought to develop a non-invasive fluid sampling device using bodily fluids such as saliva, sweat, tears, or vapor from your breath.

“This would be less invasive than even a minimally invasive technology, as they would not require inserting a needle or probe into the body,” said Klonoff.

Similar issues of accuracy remain, but there has been documented progress in this area.

Who is currently developing non-invasive glucose monitors?

Although people with diabetes continue to wait for this revolutionary technology to reach the market, hundreds of millions of dollars in funding for startups around the globe, not to mention efforts by larger, more established technology companies.

Nemaura Medical

This company has developed a device called sugarBEAT, which has received approval in Europe and has been submitted to the FDA for review in the U.S.

Sitting on your skin like a patch, sugarBEAT is a small device that measures your glucose continuously by running a slight, imperceptible electric current through your skin, which causes glucose to move within the interstitial fluid right below your skin.

Early trial data from Nemaura Medical shows that sugarBEAT is very close to the accuracy of CGMs currently available on the market.

DiaMonTech

A biotechnology startup based in Germany, DiaMonTech is currently developing three versions of its non-invasive glucose monitor.

The D-Base: A desktop device (roughly the size of a shoebox) intended for use by multiple people in a clinical setting.
D-Pocket: A hand-held device that fits in the user’s pocket or handbag, on which you press your finger for a glucose measurement.
D-sensor: An integrated sensor that can be worn as a bracelet.

All three use the same technology to gather glucose measurements, which the company coined “photothermal detection.” The sensor directs a beam of light onto the skin, which warms the glucose molecules in your skin very slightly (only around 1/1000 Celsius.) After a few seconds, the sensor gives a glucose reading based on the absorption and reflection pattern of the light.

While each of these versions is at a different point in the approval process, there is evidence that the technology does work and is approaching the accuracy level of CGMs. The three devices are still in development to improve accuracy, so they are not currently available for purchase.

Apple

The tech giant considered including a non-invasive glucose sensor in the new Apple Watch Series 7, which unfortunately did not come to fruition.

UK-based startup Rockley Photonics, one of Apple’s previous partners, had released a “clinic-on-the-wrist” health watch. However, the partnership has since been discontinued. The technology is quite similar to that used by DiaMonTech and could represent a huge addition to Apple’s health monitoring features in the near future.

In February 2023, Apple announced that it hit a major milestone in developing the technology, and has reportedly been working on it since 2009. The company has spent hundreds of millions of dollars on the effort and now believes that the technology could eventually be made available to the public.

Cnoga Medical

Cnoga is a digital healthcare startup based in Israel, which has developed a hybrid non-invasive monitor called the TensorTip Combo Glucometer (CoG). The device is referred to as “hybrid” since users must calibrate it with both invasive and non-invasive measurements for the first three days of use.

After calibration, the device is completely non-invasive. Similar to other devices, CoG emits a small amount of light through your finger, which you insert into the device. As the light signal is absorbed and reflected by the glucose in your blood, the signal projects onto another camera and processes the signals using an AI algorithm to produce a glucose value.

CoG is a small, portable device that has received CE clearance in Europe. According to research, the accuracy of the device still lags behind CGMs.

GWave by Hagar

The GWave is a non-invasive glucose monitor created by Hagar, also a startup based in Israel. It uses radio frequency waves to measure blood glucose continuously. This device has currently not received CE clearance or FDA approval.

In March 2023, the company announced early results from its ongoing clinical study, which included 20 participants. The study compared GWave readings to fingerstick measurements at various time points, yielding accuracy within a narrow glucose range (70-140 mg/dL). Hagar plans to start a larger clinical trial with 250 participants by the end of 2023 on adults with type 1 or type 2 diabetes in Israel.

Know Labs

This Seattle-based startup has developed two non-invasive glucose sensors, both of which use a patented radio frequency wave technology called Bio-RFID.

The KnowU: A pocket-size device that measures your glucose on-demand with a simple palm placement on the device.
The UBand: A continuous monitor that is worn on your wrist.

While still early in the process, data from early human trials are quite promising. When compared to fingerstick glucose measurements, the Bio-RFID measurements were reported to be well within the accuracy standards established by CGMs currently on the market.

Lassie by BOYDSense

Lassie is a prospective pocket-size device that measures glucose through the breath indirectly by measuring other compounds that the body produces from using glucose for energy.

In a presentation at the ATTD 2023 annual conference in Berlin, Bruno Thuillier, founder and chief technology officer of BOYDSense, explained that the company is currently working on an algorithm that can calculate glucose levels based on measurements of specific compounds in the breath.

Other non-invasive glucose monitoring projects include:

Lifeleaf, a continuous, real-time glucose monitor by LifePlus
Afon Technology, which is developing a wearable device for your wrist
Brolis Blood Analysis Sensor
GlucoBeam by RSP systems
K’Watch Glucose smartwatch by PKVitality

The bottom line

Of course, this list is incomplete. These are just a few of the many startups and biotechnology companies seeking to develop a non-invasive glucose monitor.

Over the last 100 years, we have progressed from measuring glucose in the urine to blood testing and fingersticks to CGMs. Much has changed in that time, from improving the convenience of taking measurements to expanding our wealth of glucose data with how many measurements we can take each day. However, the need for blood or other bodily fluids to take a measurement has been constant.

So is it hope or hype? Although it may seem that regulatory barriers squash any hopes of a non-invasive device reaching the market, the demand, motivation, and money are there to keep development going.

It will be interesting to watch which of these small companies gets the attention of one of the big players in diabetes technology; this could be a clue about which device is furthest along. The technology is improving rapidly, but it may be several more years before we see a non-invasive device on the market.

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