EXPERT INSIGHT: Diabetes Treatment: A Story of Complicated Progress and Great Potential

/ EXPERT INSIGHTS

Diabetes Treatment: A Story of Complicated Progress and Great Potential

Derek Rapp

Managing Director of

RiverVest Venture Partners

(November 2024)

Diabetes is not just a disease—it is a pandemic, affecting more than half a billion adults and children worldwide, including 38 million Americans. New data released by the CDC just last week found that nearly 1 in 6 American adults (16%) has diabetes, up from 9.7% of American adults in 2000.

The cost of diabetes at both the societal and individual level is staggering. Economists have reported that in the U.S. alone, diabetes cost our economy more than $400 billion in 2022. Comparatively, heart disease cost approximately $250 billion and cancer, $21 billion.

The cost to an individual can be life-altering, as people with diabetes are susceptible to severe health complications, including loss of vision, lower extremity amputation, kidney disease, cardiovascular problems, and more. Even people who aggressively manage their disease are susceptible to mental health challenges, reduced quality of life, and premature death.

In this Expert Insight, RiverVest Managing Director Derek Rapp discusses the progress that has been made in diabetes care over the past hundred years, the urgent unmet need for prevention as diabetes has become a global health threat, and the technological leap that one RiverVest portfolio company is taking to empower patients to take control of their own metabolic health. He also shares thoughts on the importance of the entire ecosystem that is essential to better outcomes for patients.

Diabetes by the Numbers

There are two main types of diabetes — one that is autoimmune and one that is metabolic. Both types disrupt the natural system whereby insulin transports glucose to the tissues throughout the body that require glucose as a source of energy. The fact that the glucose is not able to reach these tissues and remains essentially trapped in the bloodstream until it is released (primarily through urination) means that a person will have high blood glucose levels. Additionally, this leads to organs and muscles that are starved of their energy source, causing them to be depleted or stop functioning.

Type 1 diabetes (T1D) is a chronic autoimmune disease in which the body’s immune system attacks the insulin-producing cells in the pancreas. To survive, people living with T1D must take insulin by injection or insulin pump. With nearly 9 million people living with T1D worldwide, it is one of the fastest growing, noncommunicable, chronic health conditions on the planet. In the U.S., roughly 1.4 million adults over the age of 20 and nearly 200,000 children and adolescents under the age of 20 are living with T1D.

Type 2 diabetes (T2D) is far more prevalent than T1D. Of the 38 million Americans living with diabetes, an estimated 90 to 95 percent have T2D, a metabolic disease that is tied to diet and other lifestyle factors, genetic susceptibility, and aging. It most often develops in people older than 45, but increasingly, children, teens, and young adults are developing it too.

Prediabetes affects an additional 97.6 million Americans age 18 or older (38 percent of the U.S. population), increasing their risk of developing T2D, heart disease, and stroke.

A Century of Discovery

In 1921, in one of the greatest medical breakthroughs in history, Canadians Frederick Grant Banting and Charles Herbert Best demonstrated the reversal of diabetes by introducing an extract of pancreatic islet cells from healthy dogs into dogs with diabetes, which marked the discovery of insulin. The following year, Leonard Thompson, a 14-year-old boy dying from type 1 diabetes, became the first human to receive an injection of insulin. His blood sugar levels became near-normal, with no obvious side effects, and for the first time in history, T1D was not a death sentence.

Before insulin, the standard of care was a stringent diet with minimal carbohydrates, leading many patients with T1D to die of starvation. Seen here, three-year-old “J.L.” weighed just 15 pounds in December 1922 (left). With insulin treatment, J.L’s weight doubled in less than three months (right). Source: Lilly

In 1923, Lilly Pharmaceutical Company collaborated with Banting and Best to introduce Iletin, the world’s first commercially available insulin product. People continued to use injectable animal-based insulin for decades, and because of it, millions of lives were saved.

Throughout much of the remainder of the 20^th century, although scientists were increasingly understanding the types of diabetes (perhaps most notably, the discovery in the 1970s that T1D was an autoimmune disease and hence different from the more common T2D), the way that people with diabetes were treated remained essentially constant. People were receiving injections of animal-sourced insulin (primarily porcine). The steadier a person’s eating habits and lifestyle choices were, the more in range a person’s blood sugar would be. People lived in fear of dangerous episodes of hypoglycemia caused by an overdose of insulin that would transport too much glucose out of the bloodstream. “Dead-in-bed” syndrome was far too common.

Finally, the 1980s ushered in major advancements in diabetes care, including the commercialization of the first synthetic insulin, which offered greater consistency; the first blood glucose monitors available for home use; and the first insulin pen, which made injecting insulin simpler and more precise.

The Ames Dextrometer was the first electric color-measuring device for estimating

blood sugar levels. A 20-microliter sample was required, along with a 150-second timer to read the results.

The 1990s saw the invention of external insulin pumps and the emergence of non-insulin therapies including metformin.

More recent advancements in this century include both devices and drugs. For devices, the main innovations were continuous glucose monitors (CGM) that help a person and that person’s loved ones monitor blood sugar and hence, reduce the frightening excursions from normal range, and automated-insulin delivery systems to make glucose management more effective and less burdensome.

The most significant new drugs have been sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, for example, semaglutide (branded as Ozempic® and Wegovy®). Both classes, currently exclusively labeled for T2D, offer additional health benefits, including healthier kidneys and fewer cardiovascular issues. Most notably, the GLP-1 class is generating considerable excitement for its weight-loss properties, among many potential indications. Additionally, there are drugs that are either in development or commercially available that have been shown to delay the progression of T1D to full-scale insulin dependence.

Despite these and other innovations in diabetes management over the past century, the vexing reality is that millions of people with diabetes are not doing well, even in developed nations such as the United States. One must, therefore, ask whether it is the complexity of the disease itself or other obstacles that bear the blame.

A Multifaceted Ecosystem

As investors in biopharmaceutical and medical device innovations since 2000, RiverVest sees the healthcare landscape as a multifaceted ecosystem. From our vantage point, the discovery of a potentially transformational treatment or technology is only the beginning of its long and difficult journey toward impact.

We must consider the vital interplay of academia, industry, regulators, providers, payors, advocates, and patients themselves in determining the opportunity for impact. The types of questions we must therefore answer when contemplating an investment in a company include:

Is this product effective in addressing a significant unmet need?
Can the product be manufactured to scale in a way that leads to consistency at a reasonable cost?
What type of regulatory label will be rquired, and is there a reasonable path to achieve it?
Will payors, both private insurers and public payors such as Medicaid and Medicare in the U.S., be willing to reimburse the patient for the use of the therapy?
Are physicians likely to prescribe the therapy?
Will patients clearly understand the benefits of using the therapy? If not, is it reasonable to expect that they will buy it and stay compliant with the prescribed regimen?

A gap in any of these elements can stymie a product's success.

Device Innovation for Managing Metabolic Health

One example of a potentially significant innovation for people with diabetes is a multi-analyte wearable sensor in development by Biolinq, a RiverVest portfolio company. Biolinq has spent more than 10 years developing its breakthrough technology in partnership with leading universities and bioengineering institutions.

The company’s investigational device is a wearable sensor that is minimally invasive, easy to place, with a painless user experience, and very accurate. The device also has an integrated display that communicates real-time changes in glucose levels, even without a smartphone app or receiver. This feedback supports healthier decisions when teachable moments arise. The person with diabetes can learn how different actions—eating a handful of jellybeans or taking a 15-minute walk, for example—impact their glucose levels, enabling the person both to manage their glucose levels in real time, and to think about how perhaps to modify behaviors in the future.

biolinq sensor (investigational device)

The fact that Biolinq’s product is so user-friendly is consistent with a key theme that we are seeing now in healthcare — the empowered patient. The more the patient can understand how he/she will benefit from a product and the easier it is for the patient to use the product, the more apt the patient will be to adopt the product. Physicians can prescribe a product knowing that it is effective and poses no safety concern to the person wearing it. The fact that payors also increasingly understand that it’s good business for them to provide coverage for such a device (thereby reducing the costs of emergency hospital visits and future complications) is another positive factor. This can be a win on so many counts: people get healthier, innovation is rewarded, and burdens on society are reduced.

The Future and a Call to Action

We continue to see remarkable science that has tremendous potential. However, until we see consistently better results for patients, demonstrable through hard measures such as average HbA1c and less defined measures such as improved quality of life, we should not be satisfied.

There is a great deal of excitement now over the potential development and commercialization of cell replacement therapies and immunomodulating drugs, both areas that could represent cures for T1D. There also are new drugs and drug candidates that could significantly reduce the incidence and severity of T2D. In addition to such innovations, we must continue to ensure that all links in the chain for sound healthcare are positioned to lead to better outcomes.

So, on this World Diabetes Day, RiverVest recognizes the progress that has been made in diabetes management and disease prevention. We are grateful for the breakthroughs that have come thus far and for those that will follow, and we are hopeful that there will be an ecosystem that will help these innovations have tremendous impact, allowing people with diabetes to live happier, healthier, and longer lives.

RiverVest is honored to play our role by identifying and funding promising technologies and committing ourselves to transforming them into successful therapies across a range of clinical indications.

About Derek Rapp

Derek Rapp is a managing director at RiverVest Venture Partners, where he focuses on the firm’s investment strategy, fundraising efforts, and investor relations and serves as a liaison to St. Louis’ innovation ecosystem.

Derek serves on the board of directors of RiverVest portfolio company Biolinq, Inc., and on the boards of Research!America, Cancer Research Foundation, Cortex Innovation Community, InvestMidwest, and Israeli biotech startup WeedOUT. He also serves on the Global Mission Board of Breakthrough T1D.

Before joining RiverVest, Derek served as president and CEO of JDRF (now Breakthrough T1D), the leading global organization funding type 1 diabetes research and advocacy, and as CEO of biotech startup Divergence, Inc., which he successfully led to an acquisition by Monsanto Company. Prior to that, Derek served as director of investor relations and head of mergers and acquisitions at Monsanto.

Derek earned an M.B.A. from the Wharton School of the University of Pennsylvania and an A.B. from Brown University. His experience with JDRF, combined with his personal connection as the father of a young man with type 1 diabetes, fuels his commitment to improving patient lives through science, strategy, and innovation.

About RiverVest

RiverVest Venture Partners is a leading venture capital firm building life science companies to address significant unmet needs of patients and deliver consistently strong returns to investors. With headquarters in St. Louis and offices in San Diego and Cleveland, RiverVest accesses forward-thinking research and clinical expertise at leading institutions across the country to found and fund biopharma and medical device companies.