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Abstract

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) use in individuals with type 1 diabetes and type 2 diabetes (T2D) who are treated with intensive insulin therapy. A growing body of evidence suggests that CGM use may also confer similar glycemic benefits in T2D individuals who are treated with less-intensive therapies. Investigators are also exploring the potential use of CGM as an aid in weight management. This article reviews 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.

Introduction

Advances in continuous glucose monitoring (CGM) technologies have enabled individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) treated with intensive insulin therapy to improve the efficacy of the daily diabetes self-management and their overall glycemic control. Numerous randomized controlled trials (RCTs) and real-world observational prospective studies have demonstrated that use of CGM facilitates reduction in hemoglobin A1c (HbA1c),^1

–9 increased time in target glucose range,^1

–6 and reduction in hypoglycemia risk,^10
–12 with corresponding reductions in diabetes-related hospitalizations.^10
–12

However, use of CGM in individuals with diabetes treated with less-intensive regimens such as basal insulin only, non-insulin injectables or only on oral therapies, as well in prediabetes, has not been well studied. In this article, we explore the utility, feasibility, and potential benefits of CGM use within these populations, focusing on how CGM may be used to improve glycemic control and promote adoption of desired health behaviors.

Rationale for Expanding CGM Use

Progressive decline in glycemic control

It is well established that sustained suboptimal glycemic control leads to both the acute and long-term complications of diabetes.^13

–16 Although achieving optimal glucose control remains a primary goal of diabetes management,^17,18 a number of patients with T2D do not meet their individual glycemic targets.^19,20 In 2014, the percentage of individuals with diabetes in the United States who met their glycemic targets declined to 63.8% compared with 69.8% in 2010.²¹ During the same period, the percentage of individuals with >9.0% HbA1c increased from 12.6% to 15.5%.²¹ A more recent analysis of the T1D Exchange registry participants showed similar worsening of glycemic control between the 2010–2012 and 2016–2018, and only 37% of adults had HbA1c values of <7.5%.²²

Although blood glucose monitoring (BGM) using glucose meters remains common in T2D patients on various treatment regimens, many have struggled to show efficacy of traditional BGM in changing patient behavior or reducing HbA1c.²³ A key reason for this is that BGM only provides a single point-in-time glucose value. Patients must perform frequent self-monitoring of blood glucose (SMBG) to determine the direction and velocity of their changing glucose. Unfortunately, many individuals with diabetes perform SMBG infrequently or not at all. In a recent study of T2D adults treated with antihyperglycemic agents, Siddiqui et al. reported that 61.9% of participants reported that they did not use BGM at all.²⁴ Common barriers to BGM adherence include the cost of test strips, pain of obtaining a blood sample, unconducive workplace, and overall inconvenience.²⁵ Given that glycemic control continues to deteriorate within the T2D population,²¹ it is reasonable that both clinicians and payers begin to consider the potential clinical and economic value of CGM use by individuals with T2D who are treated with nonintensive therapy.

Hypoglycemia

Hypoglycemia remains a major barrier to achieving optimal glycemic control.²⁶ especially in individuals treated with intensive insulin regimens.^26
–28 However, the risk for hypoglycemia is not limited to multiple daily insulin injection or insulin pump therapies.^15,29,30 More than 16 million individuals with diagnosed T2D are treated with nonintensive treatments.¹⁹ Approximately, 51.7% are treated with oral or non-insulin injectable medications and 14.1% are treated with both insulin and oral/non-insulin injectable therapy.¹⁹ Because BGM in this population is often sporadic, individuals who are treated with insulin and/or sulfonylurea therapy are at significant risk for unrecognized hypoglycemia. According to the UK Prospective Diabetes Study (UKPDS) 10-year follow-up report, the increased annual risk for minor and major hypoglycemia events among obese T2D patients treated with second-generation sulfonylureas were 17.5% and 2.5%, respectively, compared with metformin therapy.¹⁵ Similar findings have been reported in observational studies.³¹

In a study of 108 T2D patients treated with basal insulin and/or sulfonylureas (n = 87) and medications not associated with hypoglycemia (n = 21), 53 (49.1%) patients experienced at least one incident of mild (<70 mg/dL) or severe (<50 mg/dL) hypoglycemia during 5 days of CGM use.²⁹ There was a significant difference in the proportion of insulin/sulfonylurea-treated patients who experienced a hypoglycemia event compared with those treated with nonhypoglycemic therapy (66.0% vs. 33.9%, respectively, P < 0.001). Importantly, whereas only 13 (24.5%) patients self-reported signs or symptoms of their hypoglycemia, 40 (75%) patients reported no awareness of their hypoglycemia when detected by CGM, (P < 0.001).

Severe hypoglycemia is particularly problematic for older adults with diabetes who are treated with insulin or antihyperglycemic therapies such as sulfonylureas. These individuals are at significantly higher risk hypoglycemia due to their age, diabetes duration, glucose variability, cognitive impairments, and higher prevalence of impaired hypoglycemia awarewness.^{27,28,30,32

–35}

Hollander et al. recently reported findings from subgroup analyses that evaluated risk factors for clinically relevant hypoglycemia in 319 elderly T2D patients (≥65 years) treated with basal insulin.³⁰ The cohort included participants from two separate trials: ELEMENT-2 (n = 214)³⁶ and ELEMENT-5 (n = 105).³⁷ The incidence of clinically relevant hypoglycemia among ELEMENT-2 participants was 36.3% and 25.2% in the ELEMENT-5 group when adjusting their insulin dosages. No differences were observed in the rate of hypoglycemia incidence according to baseline HbA1c levels.

Importantly, contrary to common belief, hypoglycemia is common at all levels of glycemic control. In a study by Lipska et al., T2D patients who achieved normal glycemia (<6% HbA1c) and those with persistent elevated glucose (≥9% HbA1c) were at the highest risk for severe hypoglycemia.³⁸

Rising health care resource utilization

In addition to the clinical consequences of suboptimally managed diabetes is the economic impact on health care systems. The global prevalence of diabetes is expected to increase, from 9.3% in 2019 to 10.2% by 2030³⁹ with associated costs estimated to be ∼$2.25 trillion.⁴⁰ Most of these costs are directly attributable to suboptimal diabetes control, including ∼$750 billion in indirect costs, resulting from the economic impact of premature mortality and work absenteeism.⁴⁰ Analysis of a report on the economic burden of diabetes in the United States showed that ∼71.3% of the $327 billion diabetes-related costs in 2017 were associated with the treatment of diabetes complications, including the hospitalizations, emergency room visits, nondiabetes prescription medications, and the costs associated with lost/reduced productivity.⁴¹

Use of CGM Beyond Intensive Insulin Therapy

Although use of CGM is recognized as standard of care for all individuals treated with intensive insulin regimens,^42
–44 particularly those at high risk for severe hypoglycemia,^43

–49 a growing body of evidence suggests that this technology might also benefit the larger population of T2D individuals regardless of their treatment regimens.^{50

–65}

Glycemic management with nonintensive therapy

Recent randomized trials have demonstrated a strong association between CGM use and significant improvements in clinical outcomes in individuals with T2D treated with nonintensive insulin regimens,⁶⁶ and non-insulin therapies.^66,67 In their study of 175 T2D adults treated with one or two daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without oral glucose-lowering medications, Martens et al. reported a significantly greater reduction in HbA1c among individuals using CGM versus BGM for an 8-month period (−1.1% vs. 0.6%, P = 0.02).⁶⁶ A similar study by Cox et al. showed numerous benefits associated with CGM (blinded mode) versus routine care in T2D adults treated with non-insulin therapy, including reductions in HbA1c (−1.11% vs. −0.1, P = 0.03) and diabetes medication requirements (P = 0.01), as well as improvements in diabetes knowledge (P = 0.001), quality of life (P = 0.01), and diabetes distress (P = 0.02).⁶⁷

Significant reductions in HbA1c, diabetes-related events, and hospitalizations in patients treated with nonintensive therapies have also been reported in recent retrospective observational studies, utilizing data from large claims databases.^62,63 In a cohort of 1034 T2D adults treated with basal insulin therapy (n = 306) or non-insulin medications, prescription of a CGM device was associated with significant reductions in HbA1c within the full cohort: from 10.1% ± 1.7% to 8.6% ± 1.8%, P < 0.001.⁶² HbA1c reductions were significant in both the basal insulin and non-insulin treatment groups: −1.1% and −1.6%, respectively, both P < 0.001. As expected, the patients with baseline HbA1c ≥12.0% (n = 181) achieved the greatest reductions. Significant reductions in acute diabetes-related events (−32.9% pt/year, P < 0.001) and all-cause hospitalizations (−14.7% pt/year, P = 0.002) were also observed among a cohort of 10,282 T2D adults treated with basal insulin or non-insulin therapy during the 6 months after acquisition of a flash CGM.⁶³

Although studies have demonstrated that persistent daily use of CGM is considered essential for intensive insulin management,^{1,2,5,11,12,68,69} intermittent CGM use with nonintensive treatment regimens therapies has also shown significant glycemic improvements.^50,56,64,65 For example, in a 40-week RCT, Vigersky et al. evaluated the long-term effects of intermittent CGM compared with BGM among T2D participants treated with diet and exercise alone or other glucose-lowering therapies except prandial insulin.⁵⁶ Participants performed four cycles of CGM use (2 weeks/1 week off) for 3 months. Investigators observed a significant reduction in HbA1c at 12 weeks among the CGM group versus SMBG group, with sustained improvement for duration of the study. Importantly, the improvement seen in the CGM group occurred without a greater intensification of medication. Within the same cohort, Fonda et al. found that intermittent use of CGM is a cost-effective option for individuals treated with nonintensive therapy. Investigators concluded that repeated use of CGM may lead to additional cost savings.⁵⁰ In an RCT of Japanese adults with T2D treated with oral anti-hyperglycemic medicines with lower baseline HbA1c (7.8%) 3-month use of CGM led to a greater reduction in HbA1c than with BGM −0.43% (P < 0.001) versus −0.17% (P = 0.124) at 6 months.⁷⁰

More recently, Bergenstal et al. assessed changes in HbA1c and treatment satisfaction within a cohort of 594 nonintensively treated adult T2D patients who participated in a comprehensive telemedicine program.⁶⁴ At an average follow-up of 10.2 months, significant HbA1c reductions were observed, from 7.7% to 7.1%, P < 0.001. The greatest reductions were observed among participants with >9.0% HbA1c at baseline. The overall score for CGM satisfaction was 4.5 out of 5. Importantly, most respondents (94.7%) indicated that they were comfortable inserting the sensor remotely with guidance from their coach and that CGM use improved their understanding the impact of eating (97.0%), increased their diabetes knowledge (95.7%) and helped them improve diabetes control when not wearing the sensor (79.4%). In a separate study,⁶⁵ it was shown that participation in the telemedicine program was also associated with reductions in diabetes-related distress (DDS) as measured by the DDS scale, specifically in the subscale score for regimen-related distress,⁶⁵ which is a risk factor for suboptimal glycemic control,^71,72 increased prevalence of complications,^73,74 all-cause mortality,⁷⁴ and poor adherence to therapy.^75
–77

Beyond Glycemic Control: Behavior Modification

Although numerous trials have demonstrated the value of CGM in improving glycemic control, a growing number of studies have also shown that use of CGM promotes both therapy adjustments and diabetes self-management behaviors.^{51,54,58,78

–82}

In a recent study, Taylor et al. investigated the effects of CGM use in conjunction with a prescriptive lifestyle modification program on blood glucose control and cardiovascular disease risk markers in 20 older adults with T2D and obesity.⁸² Participants received a low-carbohydrate diet and lifestyle plan and randomized to wear a CGM sensor in either the blinded (control) or unblinded (intervention) mode. At 12 weeks, both study groups showed similar reduction in HbA1c and lipid levels; however, the intervention group experienced notably greater reductions in body weight (−7.4 kg vs. −5.5 kg), with consistently less glycemic variability and a 40% greater reduction in diabetes medications.

Similarly, Taylor et al. conducted a review of eight RCTs (n = 5346) and three observational studies (n = 196) that assessed the impact of CGM use on HbA1c, bodyweight, and caloric intake compared with SMBG in older T2D adults.⁵⁸ CGM use promoted greater reductions in HbA1c, bodyweight, and caloric intake, with higher adherence to healthy eating, physical activity, and other self-care behaviors. Similar findings were reported in another study that investigated intermittent CGM use in T2D adults, demonstrating significant reductions in total daily calorie intake, bodyweight, body mass index, and postprandial glucose excursions, with a significant increase in total exercise time per week after 3 months.⁵¹

In a small pilot study that focused on glycemic index reduction using CGM in newly diagnosed non-insulin-treated T2D patients, Cox et al. reported significant weight loss (−7.2 kg), and decreased intake in high glycemic index food, lower total carbohydrate intake, and increases in dietary fiber for the 3-month study period.⁸⁰ These outcomes were accompanied by a 1.0% HbA1c reduction.

Allen et al. have also shown significant benefits of CGM use in promoting physical activity,⁵⁴ creating teaching opportunities,⁷⁸ and problem-solving⁸¹ in T2D adults. Similar associations between CGM use and improvements in physical activity^53,83 and dietary modifications⁵¹ have also been demonstrated in early studies.

Beyond Diabetes: Weight Management

According to current estimates, 73.6% of U.S. adults (>20 years) are overweight or obese.⁸⁴ This includes a vast majority of the estimated 88 million people aged >18 years with prediabetes.¹⁹ In addition to their significant risk for developing diabetes, overweight and obese individuals are at increased risk for several other serious diseases and health conditions, including all-cause mortality, hypertension, hyperlipidemia, heart disease, stroke, depression, osteoarthritis, certain cancers, body pain, and low quality of life.^85

–89

It is widely accepted that nutritional composition and intake are the most influential and modifiable factors in individuals who are overweight or obese. Although many individuals continue to pursue popular diet strategies and commercial meal preparation services, >60% of these individuals regain more weight than they lost within 4 or 5 years.⁹⁰

Recent research has highlighted the influence of individual biological factors on the metabolic response to different foods, which varies substantially from person to person. Approaches employing CGM and artificial intelligence (AI) to develop algorithms that can be used to develop more effective dietary approaches for weight loss and subsequent weight management are being studied. This approach is often referred to as precision nutrition, with the goal of utilizing data from numerous factors, including human gut microbiome, to predict each individual's glycemic responses to various foods.

In a recent study, Hall et al. utilized CGM to assess the frequency and magnitude of postprandial glucose excursion, the types of glycemic patterns, and how these patterns varied in 57 individuals without prior diagnosis of diabetes who were given an identical meal challenge.⁹¹ The physiology underlying dysglycemia varied with differing levels of insulin resistance and secretion among participants. Utilizing AI technologies, an analytical framework was developed that grouped participants into glucotypes, which categorize individuals based upon their specific patterns in response to various foods. Importantly, CGM revealed that individuals who are traditionally considered normoglycemic exhibited high glucose variability that exceeded glucose ranges associated with prediabetes and diabetes 15% and 2% of the time, respectively. Based on findings from this study and others,^92
–94 investigators are now using CGM, activity and sleep trackers, and a food logging app to collect data from individuals to develop the “ideal diet” for each individual.⁹⁵

Conclusions

For the past 10 years, numerous studies have demonstrated the glycemic benefits of CGM use in individuals with T1D and intensively treated T2D,^{1

–9,1

–6,10
–12} with reductions in health care resource utilization and costs.^6,7,96 There is a growing body of evidence suggesting that CGM use confers similar benefits in individuals with diabetes who are treated with less-intensive therapies.^{50

–65} Moreover, behavioral interventions that included use of CGM has been shown to improve dietary habits,^51,58,80,82 increase physical activity,^51,54 reduce bodyweight and cardiometabolic risk,⁸² and enhance problem-solving skills.⁸¹ All of these glycemic and behavioral outcomes are critical to safe and effective self-management of diabetes.

Despite the evidence supporting use within the larger diabetes population and as a potential tool for addressing the growing epidemic of prediabetes and obesity, CGM is not widely covered for patients on non-insulin regimens by Medicare, Medicaid and many commercial payers due to the current eligibility criteria adopted by U.S. government and commercial payers. These criteria are both misguided and scientifically unfounded,⁹⁷ and they limit access to this technology to the >16 million individuals with T2D who are treated with nonintensive treatments and the 88 million with prediabetes.¹⁹

Given the growing and unsustainable economic burden of diabetes in the United States and throughout the world, a more rational approach is to eliminate the medically unfounded policies that restrict access to important tools and technologies that have been shown to be effective in improving the health and quality of life of millions of people living with diabetes and other metabolic disorders.

Footnotes

Authors' Contributions

E.E.W. and S.S. wrote the article. Both reviewed the article before submission and take full responsibility for the accuracy of its content.

Acknowledgment

The authors thank Christopher G. Parkin, MS, CGParkin Communications, Inc., for editorial support.

Author Disclosure Statement

E.E.W. has received consulting fees from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Mannkind, Merck, Sanofi U.S., and Voluntis, and has acted as a speaker for Abbott, Bayer, Boehringer Ingelheim, and Eli Lilly. S.S. reports no financial conflicts.

Funding Information

Funding for the development of this article was provided by Abbott Diabetes Care.

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Evolving Use of Continuous Glucose Monitoring Beyond Intensive Insulin Treatment

Abstract

Introduction

Rationale for Expanding CGM Use

Progressive decline in glycemic control

Hypoglycemia

Rising health care resource utilization

Use of CGM Beyond Intensive Insulin Therapy

Glycemic management with nonintensive therapy

Beyond Glycemic Control: Behavior Modification

Beyond Diabetes: Weight Management

Conclusions

Footnotes

Authors' Contributions

Acknowledgment

Author Disclosure Statement

Funding Information

References