Managing diabetes has always been an enormous strain on patients and the healthcare system. According to the American Diabetes Association,¹ in 2019, 37.3 million Americans—about 11.3% of the population had diabetes. Almost 1.9 million Americans in that category had type 1 diabetes, including about 244,000 children and adolescents. Another 1.4 million new U.S. cases are diagnosed every year. And after adjusting for population and sex differences, average medical costs among people with diabetes were 2.3 times higher than what expenditures would be without the disease.

Diabetes was also the seventh leading cause of death in the U.S. in 2019, based on the 87.467 death certificates where diabetes was listed as the underlying cause of death. In 2019, diabetes was mentioned as a cause of death in a total of 282,801 certificates.

“With 422 million diabetics worldwide—and 37.5 million in the U.S. alone—the diabetes market is huge,” said Tim Steele, founder and CEO of Microspec Corporation, a Peterborough, N.H.-based extruder of custom medical parts. “Among this population, over 90% of people are diagnosed with Type 2 diabetes and this group is growing rapidly. Currently there is no cure for either Type 1 or Type 2 diabetes and there is fierce competition to develop a device/system to monitor HIC or blood sugar more efficiently and painlessly.”

This article will examine several recent innovations in diabetes monitoring and treatment technologies, as well as those in development that are a potential novel approach to treating the chronic, cumbersome disease.

Dexcom

The much-heralded Dexcom G7 continuous glucose monitor (CGM) came to the U.S. market this year following FDA approval and EU launch a few months ago.

“Dexcom G7 is the most powerful, easy to use and accurate continuous glucose monitoring (CGM) system cleared by the FDA, and we know users and healthcare providers are excited to experience these features and more with G7,” said Jake Leach, COO of Dexcom. “We delivered on our promise to bring users a next-generation sensor that is 60% smaller with an all-in-one wearable, completely redesigned mobile app, and the fastest warmup time of any CGM on the market. Reducing the warmup time from two hours to 30 minutes is a game-changer, especially for parents and loved ones of Dexcom CGM users, who can monitor glucose levels remotely via the Follow App.”

The company is working closely with insulin pump partners to integrate G7 into current and future automated insulin delivery systems. It also features a suite of customizable alerts to warn users about high or low glucose levels. Users can share information with loved ones and care teams through remote monitoring and reporting capabilities.

The G7 CGM features a 12-hour grace period to replace finished sensors. Its accompanying mobile app was redesigned and simplified and alert settings were improved to enhance discretion. The redesigned, smaller optional receiver has a more vibrant, easier to read display. It can be worn on the back of the upper arm for patients aged 2 and older, or on the upper buttocks for patients aged 2 to 17. The G7’s smaller form factor also translates to smaller plastic components and packaging to reduce waste.

“We executed a successful launch of Dexcom G7 in the EU last year and plan to bring G7 to new geographies in 2023,” said Leach. “In the U.S., we received FDA clearance in late 2022 and expect a full launch in Q1 of this year. Throughout 2023, we’ll continue to focus on building momentum, increasing access to our life-changing CGM technology, and creating a foundation of growth for years to come.”

In fact, the company proclaimed the coming U.S. launch for G7 in a Super Bowl commercial featuring musician Nick Jonas. According to the company, it launched on Feb. 17. And on the day after the Super Bowl, Dexcom revealed that Medicare will offer coverage for its beneficiaries using the next-generation G7 CGM.

The decision by the Centers for Medicare & Medicaid Services (CMS) will include coverage for type 1 and 2 diabetes patients on intensive insulin therapy. The decision doesn’t include coverage for patients with type 2 diabetes taking basal insulin, the company said. In a recent earnings call, Dexcom execs commented that they expect CMS to make that decision in the middle of this year. (Dexcom expects basal insulin users to account for about 1% of the company’s revenue in 2023.)

In the meantime, the company plans to provide a bridge program for its customers that are paying in cash while it pursues broader insurance coverage.

Tandem Diabetes Care

Tandem Diabetes’ t:slim X2 insulin pump was granted FDA clearance in February 2019. The interoperable pump delivers insulin under the skin at set or variable rates and can be digitally connected to communicate with and receive inputs from other diabetes management devices like CGMs and drug dosing commands from automated insulin dosing (AID) software. When not connected, the t:slim X2 pump can be used to infuse insulin on its own. The new type of pump was referred to as an alternate controller enabled (ACE) infusion pump—or ACE infusion pump. At the time, it was the first interoperable pump, meaning it can be used with different components that make up diabetes management to allow tailoring of therapy to individual device preferences.

A year later, t:slim X2 gained an FDA nod for Tandem’s Control-IQ technology, a hybrid, closed-loop feature to help increase blood glucose time in range (70-180 mg/dL). Control-IQ automatically adjusts insulin delivery using CGM values, along with other variables like insulin on board, to predict glucose levels 30 minutes ahead and adjust insulin correction boluses accordingly. Control-IQ also features optional settings for sleep and exercise that will change treatment values to better match the different physiologic requirements during these activities.

“When it comes to diabetes management, we don’t believe it is ‘one-size-fits-all,’” said Elizabeth Gasser, executive VP and chief strategy officer at Tandem Diabetes Care. “Our continued goal is to provide people with a portfolio of options they can choose from. Building on this commitment, the integration with Dexcom G7 CGM and the t:slim X2 pump is currently in development. Additionally, we are continuing to work with Abbott to combine Abbott’s Libre CGM technology with our insulin pumps. Our goal is to bring both to market in 2023.”

In August 2020, t:slim X2 with Control-IQ was granted expanded pediatric indication by the FDA to children aged 6 and older. The product had been previously approved for ages 14 and older. Supporting this expanded indication was a six-month study of children aged 6 to 13 using the technology that demonstrated sensor time in range increased to 67% from 53%, compared to those in the control group.

Tandem has been developing a hybrid micro-pump about half the size of the current t:slim X2 pump. The new Mobi pump has both a four-inch tubing with “pigtail” connector that goes to an infusion set and adhesive on the back to stick on the body so it can be worn in either configuration. The company had planned to submit Mobi to the FDA in 2020 but its clinical trial was delayed by the pandemic.

“We are also having continued conversations with the FDA as they review the Mobi insulin pump for approval,” said Gasser. “The Mobi pump is designed to deliver the same therapy benefits as t:slim X2 with Control IQ technology but in a smaller, discreet form factor that is fully phone-controlled. Our aim is to bring it to market in the second half of 2023. In keeping with our goal of providing people with diabetes access to options, we are always looking for ways to bring innovative therapy management solutions to market.”

In late January, Tandem acquired AMF Medical, privately-held Swiss developer of the Sigi ergonomic, rechargeable patch pump for CHF 192 million ($205.2 million). Currently under development, Sigi aims to lower the burden of diabetes via use of pre-filled insulin cartridges and compatibility with automated insulin technology.

“AMF Medical is the developer of the Sigi insulin patch pump, a tubeless insulin pump patch that is durable, rechargeable, and designed to be used with standard pre-filled insulin cartridges,” said Gasser. “The acquisition of AMF Medical allows us to accelerate our efforts to add a tubeless insulin pump to our portfolio and deliver the benefits of our AID system to more people with diabetes. The team is innovative, experienced, and shares Tandem’s deep commitment to user-centric design.”

The insulin delivery solution is expected to boost Tandem’s market opportunities for both type 1 and 2 diabetes. It also provides the company an additional pump that reduces electronic and battery waste generation.

Insulet

Insulet’s Omnipod 5 automated insulin delivery (AID) system earned FDA clearance in January 2022 for people with type 1 diabetes aged 6 and older. The tubeless AID system also integrates with Dexcom’s G6 CGM system. Omnipod 5 requires no multiple daily injections, no tubes, and no fingersticks to help manage diabetes. Omnipod 5’s SmartAdjust tool receives a Dexcom CGM value every five minutes and predicts glucose levels an hour into the future. Insulin delivery is then increased, decreased, or paused to achieve the desired and customized insulin target.

The company launched Omnipod 5 in August 2022 via pharmacy retail channels.

“This year, we will continue to advance our innovation pipeline, grow adoption of our Omnipod 5 automated insulin delivery system in the U.S., and launch Omnipod 5 in our first two international markets,” said Dr. Jim Hollingshead, president and CEO of Insulet. “We are also in the process of building a new 400,000-square-foot manufacturing facility in Malaysia, which will add to our existing production capabilities sometime in 2024.”

Omnipod 5 gained expanded indication for type 1 diabetes patients aged 2 years and older later in August 2022. To support the clearance, a study published in the journal Diabetes Care in July 2022 showed Omnipod 5 “significantly improved” time in range, and reduced HbA1c and time in hypoglycemia (<70 mg/dL) in children aged 2-5.9 years) with type 1 diabetes. Parents and caregivers of study participants also reported improved sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI).

In September 2022 Omnipod 5 won CE mark clearance as well, also for type 1 diabetes patients aged 2 years and up. It became the first CE marked tubeless, hybrid, closed-loop system that pairs with Dexcom’s G6 CGM to automatically adjust insulin and help guard against high and low glucose levels.

“We are thrilled with the type 1 community’s response to Omnipod 5, which was released this past year, and we’re excited to increase adoption of Omnipod 5 in the U.S. and begin rollout in the first European markets in 2023 and more broadly in 2024,” said Dr. Hollingshead. “Being the first tubeless, wearable, waterproof AID system, Omnipod 5 has been and will continue to be a game-changer for people with diabetes.”

Insulet’s Omnipod DASH insulin management system was cleared by the FDA in June 2018. It was built to be simple, discreet and easy-to-use and the system features Bluetooth wireless technology for connectivity to other diabetes management components. Omnipod DASH was launched in several more European markets in October 2020, and came to Canada in January 2021. The company is also working to make the technology available for type 2 diabetes patients needing insulin therapy.

“We are seeing increased interest in pump therapy from people with insulin-requiring type 2 diabetes. Our Omnipod DASH product, which has the same form factor—a tubeless, wearable, disposable Pod—has been extremely popular with people with type 2 diabetes,” said Dr. Hollingshead. “We are following this trend closely and have submitted a 510(k) to the FDA for a basal-only Pod for the type 2 market. We plan to begin U.S. commercialization in 2024.”

“We’ve also completed a feasibility study on Omnipod 5 for this patient population and presented fantastic results at ATTD in Barcelona last fall,” Dr. Hollingshead continued. “The data demonstrated that Omnipod 5 significantly improved time in range and reduced use of insulin in our trial participants. We intend to launch a pivotal trial for Omnipod 5 for people with type 2 diabetes in 2023.”

Insulet made two back-to-back $25 million acquisitions on Feb. 13 and Feb. 14 to further bolster its portfolio.

The first was assets from Bigfoot Biomedical related to Bigfoot’s pump-based, automated insulin delivery (AID) technologies. Specifically, it includes Bigfoot patents related to pumps that may be used in AID therapy. Connected injected support technology like Bigfoot Unity use smart pen caps for dose suggestions based on CGM data. Depending on the needs of the diabetes patient, it could present a better fitting option than the Omnipod 5.

On Valentine’s Day, Insulet announced the $25 million acquisition of Palo Alto, Calif.-based Automated Glucose Control’s (AGC) assets. The company develops and commercializes automated insulin delivery technology. The two companies began a license agreement and partnersip in 2016 based on patents and other intellectual property AGC licensed from the Dr. Francis J. Doyle III laboratory at the University of California, Santa Barbara.

The company also underwent a few product recalls last year for both the Omnipod 5 and Omnipod DASH systems and provided comment to MPO about the actions being taken to remedy the issues.

“The health and safety of our customers remain our top priority, and these actions were taken voluntarily with the knowledge of the FDA. No serious injuries have been reported to Insulet as a result of these issues.
For the voluntary Medical Device Correction for Omnipod DASH Personal Diabetes Manager (PDM), we are replacing the PDMs for all our customers due to reported issues, which may occur if the PDM battery is charged to full capacity or for extended periods of time. The Omnipod 5 voluntary Medical Device Correction is due to an issue with the charging port and cable. We notified customers by email with instructions on how to detect and reduce the risk of an issue with the charging port or cable.”

Fractyl Health

Fractyl Health is an organ-editing metabolic therapeutics company that aims to pioneer a new approach to treating type 2 diabetes (T2D). The company’s goal is to transform treatment from chronic blood glucose management into disease-modifying therapies that target the organ-level root causes of T2D.

As opposed to type 1 diabetes, T2D is a progressive metabolic disorder of rising blood sugar. It’s caused by two parallel, progressive disease processes: insulin resistance and insulin insufficiency. Resistance describes the body’s inability to respond to insulin and remove sugar from the bloodstream. Insufficiency describes the gradual failure of the pancreas to produce enough insulin to meet the body’s requirements. The two are interrelated and result in chronic high blood sugar levels.

According to the company, almost half of U.S. T2D patients aren’t achieving adequate glucose control today. They claim this is due to current therapies focusing on managing blood sugar symptoms rather than trying to correct the underlying disease processes in the body.

“T2D is a systemic disease, where certain organs responsible for controlling blood sugar become diseased and the progressive dysfunction of these organs causes blood sugars to rise,” said Harith Rajagopalan, M.D., Ph.D., co-founder and CEO of Fractyl Health. “It’s important to correct the function of these diseased organs rather than exclusively focus on measuring or managing blood sugar—a symptom of the disease rather than the disease itself. Our organ editing approach is designed to target the diseased organs in a minimally invasive way. It aims to correct the function of these organs, so the body can manage its own blood sugar more effectively again.”

Fractyl’s organ editing technology involves the process of targeting and modifying the duodenum and pancreas directly as a means to address T2D’s organ-level root causes. The approach identifies diseased metabolic organs and designing disease-modifying treatments to reverse the core pathology in those organs driving the disease’s organ-level root causes.

The company’s Revita product targets duodenal dysfunction via a minimally invasive endoscopic procedure. The Revita catheter is inserted through the mouth and into the duodenum and isolates the mucosa from the deeper layers of the duodenum to separate them, then hydrothermally ablates the excess surface layers of the duodenal lining. Following the ablation procedure, the duodenal mucosa regenerates, which the company believes leaves the duodenal lining revitalized and better able to function in order to potentially improve metabolic health.

“This year we will have three main goals. We plan to advance our Revitalize-1 pivotal study in insulin-treated T2D, which will be necessary for approval in the U.S.,” said Dr. Rajagopolan. “We aim to initiate a commercial pilot in Germany, where Revita already has a CE mark and reimbursement under the NUB remuneration scheme. We will also present proof-of-concept data for our preclinical Rejuva pipeline pancreatic gene therapy program.”

The company’s Rejuva novel pancreatic gene therapy platform, currently in development, aims to restore insulin production capacity in the pancreas for T2D patients. It involves an endoscopic, locally administered adeno-associated virus to the pancreas to allow local gene therapy and then enable local production of key metabolic hormones known to be necessary for proper insulin production in the pancreas’ beta cells.

Supplying the Demand

Microspec works alongside diabetes technology makers to produce critical components for their evolving products. The company specializes in extruding some of the smallest, most complex medical tubing in the industry with very tight tolerances. The company extrudes medical tubing with an outside diameter from 0.0004 inches to 0.450 inches (0.1 mm to 10 mm) to meet the demand of diabetes technology makers seeking smaller, more discreet form factors in their products.

“Diabetes technology outside monitoring blood sugar and delivering insulin has been moving forward. We first became aware of a new technology when a small Massachusetts company inquired to us about extruding highly complex tubing that would be used to perform a short outpatient procedure to cure a patient’s Type 2 diabetes,” said Steele. “The development of the tubing for the new device/procedure spanned over two years. It involved full validation of the tubes and process and much innovative and inventive modifications to our machinery and the way we extruded the parts. The relationship between MicroSpec and our client developed into a close partnership. Transparency between the two companies was nearly complete, in the interest of getting the device and technology to market faster so the millions of affected people could live free of diabetes.”

Supply chain woes continue to plague component suppliers to the medical device industry, as the hit the supply chain took during and after the COVID-19 pandemic shows no signs of slowing.

“As with any innovative device or technology, getting to market in a timely manner is a primary driving force, and navigating regulatory waters is a challenge for every device maker,” said Steele. “Supply chain issues for raw materials, spare parts, and machinery have also challenged us and pushed our lead times to unprecedented lengths. Although the labor situation shows some signs of improving, finding qualified help has gotten more expensive by about 20%. The pandemic is still a force that slows technology development today and we should not forget it practically shut everything down in 2020 and could happen again.” 

Reference

1. https://diabetes.org/about-us/statistics/about-diabetes