Emerging Landscape of Continuous Glucose Monitoring

Introduction

Diabetes prevalence continues to increase globally with current estimates at 463 million people with both type 1 diabetes (T1D) and type 2 diabetes (T2D). ¹ The overall prevalence of diabetes in the United States is ∼9%. ² The prevalence of both T1D and T2D is increasing at the rate of ∼4% annually and about 1/3 of patients remain undiagnosed. ² However, the highest concentration of diabetes, globally, is in the Middle East. ³ As expected, all patients with T1D and about 20% of patients with T2D require insulin therapy for managing their diabetes effectively during their lifetime. ⁴

Disparities in Diabetes

Diabetes continues to affect communities of color disproportionately higher. For example, the highest prevalence of diabetes in the United States is among Native Americans (14.7%), which is nearly two times higher than Caucasians. ⁵ African and Hispanic Americans also have higher prevalence of diabetes in the United States. ⁵ These populations are also at higher risk for severe diabetes complications. Approximately 50% of the Asian population in the United States is likely to be diagnosed with end-stage kidney disease. ⁶ Similarly, African Americans and Hispanic have a 3.5- and 1.4-fold higher risk of getting end-stage kidney disease and diabetes-related amputations when compared with Caucasians. ⁶

Unfortunately, Hispanic and Native Americans are much less likely to be offered new technologies like continuous subcutaneous insulin infusion (CSII/insulin pumps) and continuous glucose monitoring (CGM) systems. ⁷ However, use of technology, especially CGM, is expected to remove many of the social barriers and disparities in care for people with diabetes. ⁸

Impact of COVID-19 epidemic

Since December of 2019, the COVID-19 outbreak has affected more than 215 countries, translating to more than 183 million cases worldwide of COVID-19 at the time of this writing. ⁹ More than 3.98 million people have died from COVID-19 across the globe; however, the Americas have been most affected. There have been more than 73 million cases reported in the United States and South America, with a total of 1.9 million deaths due to the virus. ¹⁰ Although the exact prevalence of infection is currently unknown, it is commonly believed that ∼70%–80% of the population will need to be infected or vaccinated for herd immunity to be effective. ¹¹

Clinical impact

The clinical impact of COVID-19 on individuals with diabetes has been significant. Patients with diabetes (PwDs) (both T1D and T2D) face a higher risk of morbidity and mortality associated with COVID-19. ¹² The incidence of diabetes and hypertension in intensive care unit (ICU) patients with COVID-19 is almost twofold higher than in non-ICU patients. ¹² Recent United Kingdom National Health Service (U.K. NHS) data illustrate that people with T1D and poor glucose control (HbA1c >8.5%) have a 3.5-fold higher risk of death from COVID-19 than those without diabetes. ¹³ There have been some reports that the COVID-19 virus is directly related to the onset of T1D. ¹⁴

Because many localities imposed stay-at-home, safer-at-home, or other lockdown orders, most of the economy came to a screeching halt in March 2020. Unfortunately, these social-distancing restrictions have adversely affected many chronic conditions, including diabetes. Many new-onset patients with T1D delayed seeking medical advice during COVID-19 because of the risk of infection. ¹⁵ Many hospitals noted a higher number of patients presenting with diabetic ketoacidosis (DKA) because of a delay in diagnosing T1D. ¹⁶ Similar concerns were noted by many of the physicians managing diabetes during pregnancy.

Economic impact

In addition to the human suffering, the COVID-19 global pandemic has affected health care (clinical and research) enormously, with devastating consequences physically, socially, and economically. ¹⁷ For example, the Mayo Clinic reported a loss of $3.9 billion during the pandemic in 2020. ¹⁸ As it relates to diabetes, many primary care and family practices have gone out of business during this pandemic, which is unfortunate because the majority of PwDs in the United States are followed by these offices. ¹⁸

The global pandemic has also resulted in dramatic reduced gross domestic product growth and recession. ^17,19 It is almost incomprehensible to think that a viral infection brought nearly the entire world economy, including health care, travel, hospitality, and numerous other industries, to a standstill.

CGM and rapid emergence of “virtual care”

Despite the catastrophic consequences resulting from the pandemic, a silver lining may be the emergence of telehealth and virtual care as an alternative approach to delivering efficient and ongoing efficient care to PwDs. ^{20 –22} Use of telehealth technologies was facilitated by readily available and accurate CGMs (Dexcom G6, San Diego, CA; Abbott FreeStyle Libre 14-Day and FreeStyle Libre 2 [FSL2], Alameda, CA; and Medtronic Guardian sensor, Northridge, CA) and the capability to download the data remotely. ²⁰

Globally, there are more than 3 million users of Abbott Libre, about 1 million users of Dexcom G5 or G6, and about 1 million users of Medtronic Guardian sensor. ^23,24 A small number of patients have used Eversense 3-month implantable sensor in the United States. Current global estimates of net sales of all three CGMs are about $6 billion, which is likely to increase significantly and expected to double in the next 3 years. ²⁵ A significant portion of increased CGM use was facilitated by Abbott Diabetes Care reducing their CGM cost such that many patients could afford buying it directly from the pharmacy (with a provider's prescription) without going through their insurance, especially in the United States and many other parts of the world. The US Food and Drug Administration (FDA) recently cleared the Freestyle Libre 2 iOS application for CGM in patients with diabetes with optional real-time glucose alarms.

Fortunately, now, most commercial payers, Medicare and Medicaid (in many States of the United States), do cover CGM use in patients requiring insulin for their diabetes management (especially during the pandemic). It is interesting to note that many of these payers have been reimbursed for the expensive insulin pump treatment for a much longer time.

The improved accuracy of all CGMs (mean absolute relative difference <10%) expedited the reliance on CGM data by both patients and providers, and further development of multiple hybrid closed-loop (HCL) systems. The U.S. Food and Drug Administration (FDA) also authorized, on an emergency basis in the spring of 2020, the use of CGM in the inpatient setting to facilitate remote care for hospitalized patients, similar to virtual care provided to nonhospitalized PwDs. ²⁶

In many instances, most diabetes care, including patients with DKA, can be effectively managed remotely by using newer technologies like CGM, ^20,21 insulin pumps, and HCL systems. ^{27 –29} Even insulin pump and CGM initiations have been successfully initiated remotely with no adverse outcomes. ^28,29 Moreover, remote monitoring and telemedicine consults have been shown to result in similar or greater time in range (TIR) for glucose levels with no increase in time below range during the virtual care period. ³⁰

However, improvement in TIR during the pandemic was unfortunately associated with socioeconomic status. For example, in a recent study by Van der Linden et al., change in TIR was twofold higher in patients making >$150k/year compared to those making <$50k/year during the pandemic. ³⁰ The changes in TIR during the pandemic also correlated by “zip” code. ³⁰

About This Supplement

In this supplement, Bailey and Alva discuss how improvements in CGM accuracy have led to changes in daily self-management, specifically in individuals treated with intensive insulin management. ³¹ Many CGM devices no longer require confirmatory fingerstick testing by blood glucose monitoring, and two systems, FreeStyle Libre (Abbott Diabetes Care, Alameda, CA) and Dexcom G6 (Dexcom, Inc., San Diego, CA), have received clearance from the FDA as integrated devices (iCGM).

Numerous randomized controlled trials have clearly demonstrated the benefits of CGM in individuals treated with intensive insulin therapy. However, because these studies are conducted with closely controlled research settings, the results may not replicate how or if individuals will actually integrate CGM into their daily lives, potentially resulting in an overestimation of efficacy. Gavin and Bailey provide a comprehensive review of real-world, observational prospective studies that provide greater insights into the clinical effectiveness and economic impact of this CGM within the broader diabetes population. ³²

As discussed earlier, use of telehealth and remote monitoring technologies can significantly improve glycemic control in T1D and T2D patients. Patients' ability to interact remotely with their health care providers through smartphones and other communication devices can increase their access to clinical care and online coaching and support programs. Carlson et al. present a series of patient cases, in this supplement, which illustrate how remote monitoring of CGM data supported by virtual clinic visits was used effectively to provide diabetes during the COVID-19 pandemic. ³³

The availability of active alarms and alerts enables CGM users to take immediate action to mitigate current and impending hypoglycemia and hyperglycemia. However, some CGM users may be overwhelmed and fatigued with the constant interruptions caused by frequent alarms, and eventually fail to respond to them. With the recent introduction of the FSL2, patients have the option to turn off their alarms according to their individual needs and preference. ³⁴ Miller and Midyett provide a comprehensive description of the FSL2 alarm function and provide guidance to clinicians when counseling PwDs. ³⁴

Although demand for CGM in primary care settings continues to increase, many clinicians are uncertain about which devices are most appropriate for each patient. Hirsch and Miller review the features and functionality of the most recent commercially available CGM devices and provide guidance for integrating CGM use into clinical practices. ³⁵

Although the clinical benefits of CGM and other diabetes technologies are well documented, the costs of integrating these tools into clinical practice must be evaluated. In their article, Nolan and Frazzitta discuss the key factors considered by commercial payers when assessing the efficacy and efficiency of CGM in their member populations. ³⁶

Because cost is a key factor in coverage decision-making, public and commercial payers must weigh the clinical benefits against the cost of CGM utilization within their member populations. Frank et al. present findings from a budget impact analysis that assessed the cost reductions that could be achieved within the Medicaid population through use of the FSL2 system. ³⁷

Despite the growing evidence supporting CGM use in the broader T2D population (especially those requiring insulin), current eligibility criteria required by public and many commercial payers are denying millions of individuals with T2D access to this valuable technology. In their article, Kruger and Anderson present an evidence-based rationale for modifying current eligibility requirements for CGM coverage. ³⁸

As noted above, disparities in the utilization of CGM within minority and lower socioeconomic populations have been well documented. ⁸ Isaacs et al. review the scope and impact of these disparities and explore the factors that may be contributing to this issue. ³⁹

In addition to studies demonstrating the clinical efficacy of CGM use in individuals treated with intensive insulin management, ^{40 –44} a growing body of evidence suggests that this technology may also confer similar glycemic benefits in individuals with diabetes who are treated with less-intensive therapies (in patients with T2D) and in prediabetes. Wright and Subramanian explore the continuing evolution of CGM, focusing on how CGM may be used to improve glycemic control and promote adoption of desired health behaviors within broader T2D and prediabetes populations. ⁴⁵

We hope that you will enjoy and learn by reading this supplement. We want to sincerely thank all the authors who contributed in a timely manner to the supplement and Abbott Diabetes Care for providing an unrestricted educational grant to make this possible.