So you want a CGM (but don’t like needles)
How Senseonics and Nemaura Medical can make a big dent in the continuous glucose monitoring market
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Article Highlights
Continuous glucose monitors, unlike traditional blood tests like HbA1c, tell you what your glucose levels are in real-time. Keeping glucose levels in a consistent, stable range is critical.
While existing CGM manufacturers have paved the way for adoption amongst type 1 diabetics, there's practically zero traction in type 2, prediabetes, and wearable tech markets.
For CGMs to truly become mainstream, they need to be painless and hassle-free — no needles. Two potential ways to do that are implanting the sensor under the skin (Senseonics) or sticking on a skin patch (Nemaura).
Senseonics' biggest risk is failing to achieve awareness for their new product. Nemaura's risk is not getting FDA pre-market approval and executing on commercialization.
Continuous glucose monitors (CGMs) are sensors that tell you your glucose levels in real-time. It's useful for people with diabetes but has also been recently popularized as a way to track metabolic fitness for non-diabetics.
But let's be real: no one loves needles. And current CGM models require you to stick a metal filament into your skin, where it just hangs out there for 2 weeks.
I've personally tried the FreeStyle Libre and was not a fan — my arm was always sore, and I was constantly afraid of bumping into it. I'm not alone. (But if you've never had issues — amazing!)
For CGMs to truly catch on, the key question to address is: how can we make CGMs painless and hassle-free without compromising too much on accuracy and cost?
Non-invasive CGMs have become somewhat of an elusive wild goose chase over the years. Apple, Samsung, and Google are all trying their hand to no avail thus far. But today, we're going to talk about two companies with products that are much closer to becoming a reality than big tech's efforts:
Senseonics (SENS) has the first FDA-approved implantable CGM that can last for 90 days. The 180-day and 365-day versions are imminent.
Nemaura Medical (NMRD) has CE approval in Europe and the potential to get FDA premarket approval for its needle-free skin patch CGM.
If you haven't heard of Senseonics or Nemaura, maybe this post will help put them on your radar. To do that, we'll work our way up:
Why might you want a CGM?
How current CGMs work
Why CGMs still don't have widespread adoption
Implantable CGM: Eversense by Senseonics
Needle-free skin patch CGM: sugarBEAT by Nemaura Medical
The big picture
Why might you want to use a CGM?
So why would you want a CGM in the first place?
The main reason is to help you maintain consistent blood glucose levels. Quantitatively, this is known as time-in-range (TIR) — you want to avoid wild swings of blood sugar levels that are too high or too low.
The problem with infrequent blood tests done in doctor's visits — like HbA1c — is that averages can't show you the time you've spent out of range. Here are three different blood glucose profiles that all have the same HbA1c value:
Measuring HbA1c is like only seeing a stock price's 3-month average. No insight into what price it's at now, what the past trends look like — nothing. The price could be fluctuating wildly or be a static flatline, but you would never know.
With a CGM, you get to see everything in real-time.
How current CGMs work
Current CGM models can read glucose levels using a flexible metal filament around 5mm long and 0.4mm wide. This filament pokes into the body fluid around cells (interstitial fluid) just below the skin.
Glucose is found in interstitial fluid because it continuously seeps from your blood vessels and capillaries. It's not the same as what's actually in the bloodstream, but it's a decent proxy.
The sensor filament stays in place for ~2 weeks and tests glucose every few minutes. Then, a transmitter wirelessly sends the information to a monitor (either a separate reader device or smartphone app).
This category of filament-based CGMs is known as "electrochemical glucose biosensors." This means the filament is coated with an enzyme called glucose oxidase which, as the name suggests, oxidizes glucose.
Without getting in the weeds, the gist of what happens is:
Glucose + Enzyme → Reduce glucose + Electrons →
Generate electrical current → Transmit and convert electrical signal → Glucose reading
The sensors only last for a week or two because this chemistry degrades over time, lowering accuracy. By default, wear period is inherently limited by chemistry.
Filament-based CGMs, therefore, have little room for improvement — you can make it less bulky, cost less, and get rid of the need to recalibrate with regular fingerstick glucose readings. Still, two immutable facts remain: 1) they won't last more than about two weeks and 2) you still need to use a needle.
Why CGMs still don't have widespread appeal
Don't get me wrong. Current CGMs have gained major headway over the years.
As science writer Matt Hutson reports:
"CGM use in Americans with Type 1 diabetes has been growing exponentially, from 6% in 2011 to 38% in 2018 [and up to about 50% in 2020], while the price has been falling—the Abbott Freestyle Libre sensor costs $900 to $1800 per year, compared to earlier models that cost $3000 to $5000 annually, while the price of Dexcom’s CGMs has fallen around 40% over the last two model updates."
Here are quarterly sales by the four largest CGM manufacturers as of 2020:
However, CGMs still haven't caught in the mainstream. In 2018, only 2.6% of all people diagnosed with diabetes used a CGM. Even fewer people with pre-diabetes or without diabetes use it. Why?
Part of the reason why is because health insurance doesn't always cover CGMs for people with type 2 diabetes, sure.
But the main reason why is because no matter how "minimally invasive" filament-based CGMs are, needles still suck. The hassle outweighs the benefits.
For most people, the little things matter — wearing a CGM today means during those two weeks, you don't have the option of taking it off and putting it back on. So you can't freely shower, swim, or sauna without the feeling of a hard round disc on your skin. You feel more hesitant playing contact sports or partner dancing. And maybe you feel more self-conscious going on a first date or social event because you need to explain to others.
I found all of these to be true when I wore a CGM. And I constantly had to tell people, "I'm enrolled in a personalized nutrition research study. That's what this is for."
Just imagine how few people would be willing to track their daily step count or sleep if it involved using a device that was physically poking their skin.
The bottom line: People value being a normal human being and not a 24/7 cyborg. For CGMs to truly become mainstream, they need to be painless and hassle-free.
Implantable CGM: Eversense by Senseonics
So how do we get around the shortcomings of current CGM models?
One promising way is for the sensor to be implanted under the skin, which can be worn for up to 90 days. You might wonder: "wait, isn't implanting a sensor more invasive?" Hear me out.
The sensor itself is the size of a thin capsule. It uses bio-compatible materials (no metals) that don't cause allergic or immunologic responses. A transmitter does need to be taped on the skin over the sensor to receive glucose readings, but you can choose to take it off at any time —which means showers, sports, and dates without anything on your skin, if you want. Here's a closer look at how the Eversense works:
The sensor produces a fluorescence signal generated from a "reversible affinity sensing mechanism." This means that as glucose concentrations increase in the interstitial fluid, the glucose binding protein (GBP) preferentially binds with glucose rather than another substance (Dextran derivative). Thus, the amount of GBP bound to glucose correlates with the strength of the fluorescent signal.
How accurate is Eversense?
Eversense is the most accurate CGM on the market. Accuracy is quantified by a number known as MARD (mean absolute relative difference) — the lower the number, the better. Eversense's MARD is below 9%, an industry best.
Newer versions have sensors that last even longer (180-day version already approved in Europe, FDA approval is imminent this year).
By 2024, Senseonics hopes to have a CGM that can be worn for up to 1 year, requiring no external transmitter on the body. This will be a killer product that will catapult CGM use in diabetes care.
Risks and shortcomings
The biggest hurdle I see for Senseonics is establishing product awareness and widespread adoption. The CEO himself acknowledged this in a recent interview:
"Awareness is the key issue for Eversense as a new product... We have [through Ascensia] a dedicated force just focused on CGM sales. 25 sales reps… growing close to 100 sales reps over the next 5 years."
[Senseonics CEO: H.C. Wainwright Conference]
As an interested CGM user myself, the biggest drawback to implantable CGMs is that it requires a doctor to implant the sensor for you in an in-office procedure (procedure costs ~$200-300). So Senseonics is more strictly for people with diabetes, and specifically those who use insulin. It will have a hard time finding traction with health-conscious people looking to track their glucose levels to optimize their health. This is where the next product I talk about may find its foothold.
Needle-free skin patch CGM: sugarBEAT by Nemaura Medical
The holy grail of glucose monitoring is non-invasive CGM — with no needles or implanted sensors. But it's been an arduous quest so far.
A potential contender to win in this space is Nemaura Medical. sugarBEAT is a peel-and-stick skin patch that can be worn for up to 24 hours. This allows you to decide whether you want to use it every day or on intermittent days, unlike current CGMs, which you have to wear for 10-90 days 24/7.
The sugarBEAT is expected to cost one-fifth of the current cost of CGMs at $30/month compared to competitors at ~$180/month.
In May 2021, Nemaura announced receipts of a purchase order for 5,000 sugarBEAT transmitters and 200,000 sensors to distribute in Europe (where it is a CE mark approved Class IIb medical device). More will be ordered, depending on customer demand.
In the United States, they launched a non-regulated program called proBEAT which targets people with type 2 diabetes and health-conscious consumers. This is a brilliant move because there is a huge untapped market of proactive wellness CGM tracking:
“We believe integrating SugarBEAT data into the leading health and fitness apps will help to expand our target market among health-conscious consumers... which will assist in understanding how diet, sleep, stress, exercise and other lifestyle factors can impact glucose levels. Given SugarBEAT is non-invasive, we believe it is uniquely placed amongst CGMs to appeal to the health-conscious consumer market.” [Nemaura VP of Strategy, Dr. Fred Schaebsdau]
The CGM market goes far beyond what is currently being addressed today. Startups like Levels Health have already shown the demand for proactive wellness CGM tracking. Non-invasive CGM will accelerate this movement by making it more attractive to a lot more people.
How does the sugarBEAT sensor work?
The sensor patch works by passing a mild current across the skin. This current pulls the glucose from the interstitial fluid towards the top layer of the skin. The technique is called "reverse iontophoresis."
But reverse iontophoresis was unsuccessfully tried before back in the early 2000s — the first FDA-approved CGM was a non-invasive wristwatch called GlucoWatch. It was pulled in 2007 because it basically burned people's skin. The manufacturer was dissolved. It's unclear how the sugarBEAT proprietary platform is different and safer than GlucoWatch, so while I'm curious and optimistic, I'm also a bit weary. It's encouraging that no device-related adverse events were noted, but these clinical studies have yet to be published.
How accurate is sugarBEAT?
Early clinical studies have cited a MARD of 11.92%. Not industry-leading accurate, but passable, especially for users who don't use insulin. It is worth noting though that accuracy appears to drop when glucose levels go below 80 mg/dL, which can be a big problem for diabetes patients whose medical decisions rely on these glucose readings.
Risks and shortcomings
A lot is riding on whether Nemaura gets pre-market approval by the FDA this year. PMA approval has been talked about since... forever ago. The pandemic added further delays with higher priority given to COVID-19 related applications. An SEC report stated that the FDA confirmed that they would recommence their review of Nemaura's PMA application in April 2021.
Generally speaking, getting FDA clearance is harder than CE clearance since it requires proof of both safety and effectiveness. Obtaining an FDA approval is not a home run for Nemaura, but it would be a big win. However, the lower accuracy of sugarBEAT (especially in low/high glucose ranges) may make approval difficult.
It's also unclear how their go-to-market strategies are going for their proBEAT wellness program — they've been talking about marketing to health-conscious consumers since 2019. Yet, CGM startups like Levels and SuperSapiens (which only use filament-based CGMs) seem to be running circles around Nemaura's execution thus far.
The big picture
The bottom line is needle-free CGMs are incredibly valuable because people value flexibility and convenience. So whoever emerges as the winner here will be richly rewarded.
Eversense is well-positioned to become the leading CGM solution for insulin-using diabetics due to its industry-best accuracy and months-long wear period. In addition, their planned fourth-generation CGM which can be worn for up to 1 year with no external transmitter on the body will catapult the use of CGMs in diabetes care.
On the other hand, sugarBEAT is likely best suited as a wearable health tech product. Not being approved as a medical device is often considered a negative, but I think they will find a bigger market in the wellness category anyway. Startups like Levels Health have already evangelized the concept of "metabolic fitness" for everyone, making CGMs the Equinox of wearable health tech. If sugarBEAT can smartly capitalize on this movement, they'll strike big.
Lastly, building an ecosystem of proactive wellness tracking — with glucose monitoring in the epicenter — is a huge untapped market that most people don't realize. I'll show you why in a future post.
Thank you to @DrTranBioSci for giving this draft a read before posting! Find me on Twitter @healthwealthgen
Comment below if you’d like me to do a future deep dive on Senseonics and/or Nemaura, what I learned as a research participant of the PREDICT 2 study, or anything else you'd like to see. Your feedback helps me make this great.
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Christina