Shopping Cart

BACKGROUND

The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) established the benefits of tight glucose control in reducing microvascular complications of type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D), respectively.^1,2 To achieve this level of control, the use of multiple daily insulin injections (MDIs) is the mainstay of therapy for patients with T1D and may be used in individuals with T2D who do not meet established treatment goals on other therapies.³ MDI regimens typically consist of 1 to 2 injections of long-acting insulin daily, along with 3 or more injections of rapid- or short-acting insulin analogs. Intensive insulin regimens are required for those with T1D caused by the autoimmune destruction of insulin producing beta cells in the pancreas. Patients with T2D typically progress to intensive insulin therapy after treatment failure with non-insulin glucose-lowering therapies or with long-standing disease that is traceable to impaired insulin secretion along with insulin resistance.³ While intensive insulin regimens allow for achieving tight glucose control, they are associated with risks, including hypoglycemia^1,2 and weight gain.² Continuous subcutaneous insulin infusion (CSII), often referred to as insulin pump therapy, is a method for intensive insulin delivery for those with either T1D or T2D and has been associated with a reduced risk of hypoglycemia for those with T1D.⁴ Insulin pump use has also been linked to an improved health-related quality of life (QoL) for patients with either T1D⁴ or T2D.⁵ It is estimated that approximately 20% of individuals with T1D utilize insulin pumps in the United States (U.S.).⁶ Fewer people with T2D currently use insulin pumps in the U.S., perhaps because of less available evidence evaluating insulin pump use in this patient population versus those with T1D. The use of insulin pumps in those with T2D, however, is on the rise.

Frequent self-monitoring of blood glucose (SMBG) is an additional management component in achieving tight glucose control. SMBG is recommended for individuals on intensive insulin regimens to guide daily treatment decisions, including insulin doses, carbohydrate intake, and detection of hypo- and hyperglycemia.⁷ Adherence to SMBG, however, is limited by a variety of factors that encompass cost, perceived pain, and low self-efficacy.⁸ With intensive insulin regimens, utilizing MDI or insulin pump therapy, glucose variability can be common with modifications in food intake and physical activity. That type of variability has been associated with an increased risk of vascular complications for those with either T1D or T2D, independent of the glycosylated hemoglobin (A1C) level.⁹ Use of continuous glucose monitoring (CGM) devices, which provide interstitial blood glucose (BG) values continuously while the sensor is worn, can better detect short-term glucose variability and have revolutionized the understanding of the role of daily glucose fluctuations.¹⁰

Most recent figures from the CDC estimate that 30.3 million people (9.4% of the population) in the U.S. have diabetes.¹¹ With the population of people with diabetes continuously growing, it is important for health care professionals to be quite familiar with insulin pumps and CGM technology to assist patients who use these devices in diabetes management.

This program’s purpose is to provide an overview of the use of insulin pumps and CGM instrumentation for the management of T1D and T2D. The program will also review currently available insulin pumps and CGM devices, describe their advantages and disadvantages, and determine appropriate candidates for such technologies. The program will conclude with key counseling points to assist insulin pump and CGM-model users in practice.

INSULIN PUMPS

The first insulin pump was designed in the early 1960s by Dr. Arnold Kadish and was so large that it had to be worn as a backpack (Figure 1). Insulin pumps were initially evaluated as insulin delivery devices in the 1970s^12-14 and deemed acceptable alternatives to conventional insulin injection therapy for those with T1D in the early 1980s.¹⁵ The first commercially available pump was the AutoSyringe, which was also referred to as the “Big Blue Brick” because of its large size. Early insulin pump therapy was limited to those with difficult-to-manage cases of T1D and was inconvenient because of the large, obtrusive devices that sometimes required a screwdriver for dosage adjustment.¹⁶ Insulin pumps were designed to mimic physiologic insulin delivery as closely as possible. For individuals without diabetes, the beta cells of the pancreas secrete insulin at variable rates throughout the day in response to variations in glucose levels. While the body is fasting, insulin is released in low levels, which is often referred to as basal insulin secretion, and regulates glucose uptake in peripheral cells and suppresses hepatic glucose production. Basal insulin also varies throughout the day in response to changing blood glucose levels, physical activity, and other hormones, such as glucagon, amylin, and glucagon-like peptides. During food intake, insulin secretion from beta cells is increased in response to rises in glucose. Postprandial insulin secretion occurs in 2 phases. The first phase is a rapid release (bolus) of stored insulin from pancreatic basal cells, while the second is a gradual release over 1 to 3 hours in response to BG levels.¹⁷

Insulin pumps mimic physiologic insulin release by providing continuous insulin administration throughout a 24-hour period. Insulin pumps deliver continuous amounts of injectable rapid-acting insulin (e.g., lispro, aspart, glulisine) that replicate basal insulin secretion. The basal delivery rate can be varied throughout the day to respond to differing levels of insulin sensitivity. Different basal delivery programs can be set to provide tailored coverage for circumstances when insulin needs may change (i.e., weekends versus weekdays). During mealtime or snack intake, boluses of insulin can be delivered to cover carbohydrate consumption. Bolus delivery only occurs when activated by the user, thereby allowing for flexibility in meal timing and content. Many current insulin pumps contain bolus calculators that assist with calculating mealtime insulin doses based on preprogrammed carbohydrate ratios (the amount of insulin required to cover a specific amount of carbohydrates), insulin sensitivity factors (the amount of BG lowered by delivering 1 unit of insulin), and glucose targets. In addition to preprogrammed basal rates and bolus calculators, insulin pumps also allow for temporary increases or reductions in basal rates. Increases in basal rates may be needed during periods of illness or when insulin resistance is common, such as the early morning hours with the “dawn phenomenon.” Decreased basal rates can be programmed during times of increased physical activity or to prevent hypoglycemia. Insulin delivery can also be suspended for periods of vigorous exercise or during hypoglycemic episodes. Prolonged suspension (more than 2 hours), however, can lead to hyperglycemia or ketosis in those with T1D.¹⁸

Pump Components, Features, and Currently Available Devices

Current insulin pumps are pager-sized, lightweight, battery-driven devices that can adhere directly to the skin (patch pump) or be worn in a pocket or pouch (traditional pump). Insulin delivery with both types of pumps occurs through a small catheter that is inserted directly into the skin and kept in place with adhesive (Figure 2). Patch pumps are generally operated remotely by a personal digital assistant (PDA) that allows the user to program bolus doses or change basal insulin delivery. Traditional pumps are connected by plastic tubing that attaches to a subcutaneous (SC) catheter (infusion site) that adheres to the skin. Traditional pumps can be temporarily disconnected for such activities as showering, sexual activity, swimming, and/or dressing. Insulin inside the pump is stored within a cartridge called a reservoir, which holds varying amounts of insulin, depending on the pump model. Reservoirs are usually filled from a standard insulin vial that uses a detachable syringe and plunger. Patch pumps include the reservoir and the catheter, so they do not require tubing for connection (i.e., tubeless). With a traditional pump, plastic tubing connects the filled reservoir to the infusion site.

Infusion sites selected for insulin delivery are similar for insulin injected either with a pen or syringe (Figure 3). The location of the infusion site should be changed with each new insertion (the length of insertion varies based on the pump) to prevent infection, scarring, and lipohypertrophy. There are several infusion sets available with varying compatibility between pump models. Infusion sets may contain a steel or soft, flexible, plastic cannula, which stays below the skin after insertion. Several styles of soft cannulas are available that can be inserted in vertical (90°) and variable-angle modes. Insertion of the infusion sets can be manually driven by the user or automatically inserted with a device, depending on the type selected. Cannula lengths can also vary between 6 and 10 mm, with shorter lengths recommended for children or those with a lower body mass index (BMI). Tubing attached to the infusion site is available in an assortment of lengths to accommodate different body sizes and allow the user to place the pump in various locations.

Current insulin pump devices have a variety of features, including ranges in bolus and basal insulin delivery and alarms for low battery, blocked delivery, or nearly empty reservoirs. Some pumps may contain a food database that stores nutritional information about common foods or allows for wireless connection with a BG meter. Most models also keep track of active insulin, which can prevent insulin stacking and hypoglycemia when delivering multiple correction boluses. Insulin stacking can occur when multiple injections of short- or rapid-acting insulin are given in succession, which can lead to accumulation of mealtime insulin that places the patient at increased risk of hypoglycemia.¹⁹ Data from certain insulin pumps can be downloaded to computer software using a USB connection, which can help HCP’s interpret a patient’s progress. Insulin pumps can also be integrated with CGM devices.¹⁸ With the rise of CGM instrumentation, certain insulin pumps are now integrated with CGM technology. The first “closed loop” insulin pump commercially available that can alter insulin delivery based on CGM data is the Medtronic MiniMed 670G system. The system was approved in September 2016 as the first hybrid closed loop system that monitors glucose and automatically adjusts delivery of basal insulin based on the user's glucose readings.²⁰ The device is currently approved for the management of T1D in persons 7 years or older. The MiniMed 630G with SmartGuardis a newer pump that has similar features to the previously available MiniMed 530G with SmartGuard. This pump includes a threshold-suspend feature suspending insulin delivery for up to two hours when hypoglycemia is detected. Additionally, the T:slim X2 insulin pump was approved in August 2017 as the first-sensor augmented pump that allows users to make treatment decisions without confirmatory fingerstick testing due to its integration with a Dexcom CGM.²¹

The ADA publication Diabetes Forecast issues a series of Consumer Guides each year. For a detailed description of currently available insulin pumps and their features, please visit the following link: http://www.diabetesforecast.org/2020/02-mar-apr/consumer-guide-2020.html.

Advantages and Disadvantages of Insulin Pump Therapy

Several meta-analyses of randomized, controlled trials (RCTs) in those with T1D demonstrate insulin pump therapy substantially improves glycemic control versus MDIs.^4,22-24 Average A1C reductions range from 0.3% to 0.6% versus MDI regimens and appear to be greater with higher baseline A1C levels.^24,25 Improvements in A1C occur despite reductions in total daily insulin doses^4,22 and reductions in the frequency of severe hypoglycemia.^4,23,25 Those with high levels of severe hypoglycemia on MDI regimens may have the greatest reduction in frequency of these episodes when switching to insulin pump therapy.²⁵ Several studies have also noted less glycemic variability with insulin pump therapy versus MDIs in those with T1D.^26,27 Individuals using or switching to insulin pump therapy also report improved QoL and greater treatment satisfaction versus MDIs.^4,27-29 A recent meta-analysis by Roze and colleagues evaluated cost-effectiveness studies comparing insulin pump therapy with MDIs and found that pump therapy is a cost-effective option for people with T1D and poor glycemic control or problematic hypoglycemia with MDIs.³⁰

There is a smaller body of evidence evaluating the use of insulin pump therapy in those with T2D. A meta-analysis by Monami and colleagues, including 4 RCTs comparing insulin pump therapy with MDIs for at least 12 weeks, concluded that insulin pump therapy did not yield any substantial improvement in A1C or differences in hypoglycemia rates versus MDIs.³¹ The Insulin Pump Treatment Compared with Multiple Daily Injections for Treatment of Type 2 Diabetes (OpT2mise) trial is the largest RCT to date evaluating insulin pump therapy versus MDI in those with T2D.³² This trial evaluated use of insulin pump therapy versus MDIs in 331 patients with poorly controlled T2D despite MDIs. In those randomized to insulin pump therapy, A1C was significantly reduced versus those continuing on MDIs (mean difference -0.7%, (95% confidence interval [CI], -0.8 to -0.4%); P < .001). Those using insulin pump therapy achieved this reduction in A1C despite a lower mean total daily insulin dose with no differences in hypoglycemia between groups. Only 1 study has demonstrated a significant improvement in treatment satisfaction with insulin pump therapy in those with T2D.³³ Cost-effectiveness of insulin pump therapy for patients with T2D has not been evaluated and is a desired area for future research.

Because only rapid-acting insulin analogues are used in insulin pump therapy, interruption in insulin delivery due to pump malfunctions may increase the risk of diabetic ketoacidosis (DKA), especially for those with T1D. However, in clinical practice, the risk of DKA appears to be similar between insulin pump use and MDIs, perhaps because of the necessity for more frequent glucose monitoring with pump therapy.³⁴ Infusion-site reactions to the adhesive or the cannula may occur, although the frequency of these issues is not well-reported. Localized skin infections can develop at the infusion site but are rarely serious.³⁵ While today’s insulin pumps are quite technologically advanced, malfunctions in pump operation (e.g., blockages in insulin delivery, dislodgement of infusion sites) can still occur, requiring users to troubleshoot unexpected hyperglycemia. Insulin pump therapy can be costly, with the price of the device averaging $5000 without insurance coverage. Infusion sets and reservoirs must be purchased for the duration of pump use and they are typically priced at approximately $1500 annually out-of-pocket. Insulin pump therapy is covered by most insurers for eligible patients; however, out-of-pocket costs should be discussed prior to beginning therapy.

Candidates for Insulin Pump Therapy

While insulin pump therapy may have distinct advantages over MDIs, the use of these pumps is not appropriate for every patient with insulin requiring diabetes mellitus. The ideal candidate for pump therapy is a patient with T1D or insulin deficient T2D who takes at least 4 insulin injections daily, performing SMBG frequently (4 or more times daily), is motivated to achieve tighter BG control and is willing and intellectually able to manage the complexity of insulin pump therapy initiation and maintenance.³⁶ Eligible individuals should actively engage in diabetes self-management through frequent SMBG, carbohydrate counting, and adjustment of insulin doses through use of carbohydrate ratios or insulin sensitivity factors. Candidates should also be prepared to troubleshoot issues with insulin pump operation and unexplained hypo- and hyperglycemic events. The American Association of Clinical Endocrinologists (AACE) Insulin Pump Task Force has published recommendations for suitable insulin pump-user characteristics based on the available evidence and clinical experience with these devices (Table 2). Cost and insurance coverage of insulin pump devices and supplies should be discussed prior to initiation of therapy. For Medicare-eligible patients, insulin pumps are covered as durable medical equipment (DME) through Medicare Part B. For certain insurance companies, including Medicare, a C-peptide level may have to be measured to determine absolute insulin deficiency. C-peptide levels can be calculated to estimate endogenous insulin production. Low or absent C-peptide levels indicate lack of insulin production.³⁶

The American Diabetes Association (ADA) provides the following recommendations regarding insulin pump therapy:³⁷

• Most adults, children and adolescents with T1D should be treated with intensive insulin therapy with either multiple daily injections or an insulin pump.
• Insulin pump therapy may be considered as an option for all children and adolescents, especially in children under 7 years of age.
• Automated insulin delivery systems may be considered in children (>7 years) and adults with T1D to improve glycemic control.

When considering appropriate candidates for an insulin pump, certain patient characteristics may not lend themselves well to insulin pump use despite a clear medical indication for therapy. Those unable or unwilling to use MDI or frequent BG monitoring may have difficulty with the rigors of insulin pump therapy. Patients who have reservations about pump usage interfering with lifestyle (e.g., contact sports or sexual activity) or who have unrealistic expectations of pump therapy (e.g., belief that insulin pumps take over diabetes management from the individual) may not be appropriate candidates. Finally, those with a history of serious psychological or psychiatric conditions (e.g., psychosis or depression) that compromise the ability to engage in self-care may not benefit from insulin pump therapy.³⁶

OPPORTUNITIES FOR THE PHARMACIST

With the prevalence of diabetes in the U.S. growing along with evidence supporting the use of insulin pumps as providing potential advantages in specific patient populations, there is a great opportunity for pharmacists to interact with insulin pump users. While there are few published studies evaluating pharmacists’ involvement in insulin pump management, models for this type of practice may be possible in community pharmacies or ambulatory care settings.³⁸

Another area of potential value of the pharmacist is in the inpatient setting. With the use of CSII (as well as continuous glucose monitoring [CGM]) growing, there will undoubtedly be an increased need for inpatient management of patients using these devices.³⁹ The ADA currently advocates for allowing patients able to successfully manage their devices be allowed to continue to do so while hospitalized. This creates a need for institutions to create clear policies and procedures regarding inpatient use of CSII and CGM.³⁹ Further research, however, is needed to determine if CSII and/or CGM use in the hospital setting result in improved clinical outcomes when compared to traditional approaches of insulin delivery and glucose monitoring.³⁹

When patients are started on insulin pump treatment, they are initially provided with technical instruction about the safe use and operation of the apparatus by a pump trainer certified by the manufacturer. After initiation of pump therapy, individuals are typically followed closely to optimize basal rates and bolus doses, evaluate episodes of hypo- and hyperglycemia, and discuss problem-solving for pump-related competencies. Ongoing management of insulin pump therapy involves adapting insulin delivery to various circumstances, including exercise and acute illness as well as troubleshooting unexpected hypoglycemia or hyperglycemia and mechanical issues with the pump. Insulin pump users may seek assistance from the pharmacist when picking up insulin or other supplies from the community pharmacy. A list of counseling points for the pharmacist to offer insulin pump users is provided in Table 3.

While ongoing insulin pump management is primarily performed by endocrine specialists, there are several ways in which pharmacists may pursue greater involvement in this clinical area. Pharmacists who work under a collaborative practice agreement may assist health care providers with adjusting insulin doses, educating patients, and monitoring pump users. Pursuing certification as a Certified Diabetes Educator (CDE) or a Board Certified Advanced Diabetes Manager (BC-ADM) may provide opportunities for pharmacists to further assist with insulin pump management, and they may also become insulin pump trainers.³⁸

CONTINUOUS GLUCOSE MONITORING DEVICES

SMBG is an important component of diabetes management, allowing patients to evaluate their response to therapy and helping them determine whether their glycemic targets are being achieved.⁷ There have been significant developments in the technology of BG monitoring over the past 4 decades. Following the discovery of insulin in 1921, the development of improved blood glucose testing systems was under way. Prior to 1970, glucose monitoring consisted of urine glucose and ketone determination. However, urine glucose testing presented limitations, as results may be affected by fluid intake and urine concentration and do not always correlate with plasma glucose concentrations. Therefore, BG testing became the preferred method of glucose monitoring. The first blood glucose monitor became available in the U.S. in 1970, when Ames developed an instrument to produce BG results using reflectance photometry.⁴⁰ This meter was only available for doctors’ offices and hospital emergency departments. Interest in diabetes management continued to intensify in the late 1970s because of the introduction of the A1C test as a marker of glucose control and the start of the UKPDS in 1977. The Glucometer I was the first glucose monitor marketed for home use, becoming available in 1981. Toward the end of the 1980s, enzyme electrode strips were introduced, which used electrochemical principles to measure BG, eventually replacing reflectance photometry.⁴⁰

The concept of CGM was first developed by Updike and Hicks in 1967 using animal models.⁴¹ But it was not until 1999 that the first CGM device – the GlucoWatch Biographer (which is no longer available) – was approved by the U.S. Food and Drug Administration (FDA) and made available in the U.S. for retrospective use only.^41,42 Since then, there have been significant advancements in the technology of such instrumentation. All CGM models currently available operate in real-time, thereby allowing users to review information as glucose readings are taken. In recent years, CGM devices have also evolved to interact with insulin pumps.⁴¹

CGM Components, Operation, and Potential Features

A CGM device typically consists of a glucose sensor, a transmitter, and a receiver. The sensor is a probe that is inserted subcutaneously and measures the amount of glucose in the interstitial fluid via an electrochemical reaction. Sensors may range in size from 6 mm to 15 mm and are typically inserted into the abdomen, back, or buttocks. These sensors are removed and replaced by the user after 3 to 10 days of wear, depending on the apparatus.^43,44 The transmitter is secured to the sensor and is responsible for transmitting information about measured interstitial glucose to the receiver via radio frequency. The receiver receives information from the transmitter and is typically the size of a pager and can be worn on a belt, in a pocket, or carried in a purse or backpack.⁴⁴ Some CGM-device manufacturers have also begun integrating Bluetooth technology into their devices so that data may be viewed remotely from a different device.

Upon insertion of the sensor, many systems require a calibration period, or warm-up period, during which the sensor does not provide any glucose readings. This length of time varies for each CGM device and lasts approximately 2 hours. Following this, the sensor will transmit a glucose reading every 1 to 10 minutes.⁴³ The receiver will display sensor glucose values in addition to graphs that depict glucose trends.⁴⁴ In addition to real-time glucose readings, CGM devices provide short-term and long-term retrospective data. These devices also allow users to set alarms that alert them to hypo- or hyperglycemic episodes as well as alarms to indicate rapid changes in glucose (rate alarms).⁴⁵

Glucose readings obtained from CGM devices are intended to be used in conjunction with conventional BG monitoring. Per the FDA, CGM devices should be calibrated (those that require calibration) with BG meters and treatment decisions, such as adjustments to insulin doses, should be based on readings from a BG meter.⁴⁶ The CGM instrument should be calibrated following the initial warm-up period and at other points during the sensor’s life. Most available devices require calibration 1 to 2 times per day, and the user must enter (or confirm if transmitted automatically from the glucometer) the value into the CGM receiver.⁴⁴

More recently, CGM systems that do not require fingerstick calibration have been introduced to the market. The Dexcom G6 system was approved in March of 2018.⁴⁷ The G6 does not require fingersticks for calibration or confirmation for treatment decisions. Sensor life has been extended to 10 days from 7 days with the Dexcom G5. The system has also been re-designed with a slimmer sensor and a one-touch sensor applicator that allows for automatic versus manual insertion. The FreeStyle Libre was approved in September 2017 as the first "intermittently scanned" CGM system.⁴⁸ Unlike other CGM systems, the FreeStyle Libre does not continuously communicate with a receiver. Instead, the user must swipe the receiver across a sensor that is worn on the back of the arm to get a reading. Sensors last up to 10 days and the system is approved for use by adults age 18 and over. Daily calibration with fingersticks is not required as each sensor comes pre-calibrated.

Currently Available Models

 As mentioned above for insulin pumps, the ADA publication Diabetes Forecast issues a series of Consumer Guides each year. For a detailed description of currently available CGM systems and their features, please visit the following link: http://www.diabetesforecast.org/2020/02-mar-apr/consumer-guide-2020.html.

Benefits and Limitations to CGM

The effect of glycemic control in reducing diabetes complications has been well-established in major clinical trials. These trials included SMBG as part of the interventions to control glucose, demonstrating that SMBG plays an important role in the management of diabetes.⁷ Conventional SMBG using finger-stick glucose measurements has some limitations, including failure to detect nocturnal or asymptomatic hypoglycemia, lack of information regarding glucose trends, and requirement for multiple blood samples daily.⁴⁹ CGM data can be used in conjunction with SMBG to better evaluate glucose fluctuations throughout the day. Employing on-screen graphs and glucose trend arrows, users can visualize trends and understand the effect of food, medications, exercise, and stress on glucose. These data are important in allowing users to respond to out-of-range BG values. Most CGM devices also allow for downloading retrospective data, which can be utilized to identify consistent patterns in glucose levels and allow for modification of medications or lifestyle.⁴⁵

Data suggest that consistent use of CGM models may modestly improve glycemic control for those with T1D or T2D.⁵⁰ In a meta-analysis of 19 trials of adults and children with either T1D or T2D (1801 patients), CGM was associated with a significant reduction in mean A1C in adults with T1D or T2D compared with SMBG (mean difference of -0.50% [95% CI, -0.69 to -0.30] and -0.70 [95% CI, -1.14 to -0.27], respectively).⁵¹ There was no significant effect found between children and adolescents. In another meta-analysis of 14 trials of T1D pediatric and T2D adult patients (1045 individuals), CGM was not more effective than SMBG alone in reducing A1C (mean difference of -0.13% [95% CI -0.38% to 0.11%]) in pediatric patients with T1D. In contrast, patients with T2D using CGM experienced a significant reduction in A1C compared with SMBG alone (mean difference -0.31% [95% CI, -0.6% to -0.02%]).⁴⁹ One of the largest trials included in both meta-analyses was a multicenter trial completed by the Juvenile Diabetes Research Foundation (JDRF) Group that compared CGM with SMBG in 322 adults and children receiving intensive therapy for T1D (an insulin pump or at least 3 daily insulin injections).⁵² In this study, patients were stratified into 3 groups according to age (8 to 14 years of age, 15 to 24 years of age, and older than 25 years of age), and the primary outcome was a change in A1C at 26 weeks. Results showed that A1C modifications varied according to age group, with a significant difference in A1C that favored CGM over SMBG in patients older than 25 years of age (mean difference -0.53% [95% CI -0.71 to -0.25]). There were no significant between-group differences among the other age groups studied.

Hypoglycemia can be an obstacle to achieving glycemic goals, especially in those on intensive insulin regimens. The usefulness of the CGM for detecting hypoglycemic episodes has also been documented in the literature. Both T1D and T2D patients using CGMs have been shown to more likely to recognize hypoglycemic events, resulting in less time spent in the hypoglycemia range.^53,54 In a 6-month extension of the JDRF study that included 83 adults with T1D, there was a decline in severe hypoglycemic events associated with CGM use over a 12-month period.⁵⁵ This suggests that with continued use of CGM devices, patients learn about their glucose trends and when to set appropriate alarms, so they are often better able to determine and avoid hypoglycemic episodes.

Although CGM technology appears to help improve glycemic control and reduce hypoglycemia, there are several limitations to these devices that must be considered. CGM accuracy is not equivalent to that of conventional glucose meters, and glucose values obtained from CGM devices may vary from fingersticks by 10% to 20%.⁴¹ This is partly due to a physiologic lag time between BG and interstitial glucose levels of approximately 5 to 10 minutes.^41,45 Therefore, glucose values obtained via CGM are lower than actual plasma glucose when BG is rapidly rising and higher than plasma glucose when BG is rapidly falling. It is for this reason that CGM results must be calibrated with fingerstick testing (with the exception of those approved for use without fingerstick calibration). Reliance on CGM data alone may result in patients overtreating for hypo- and hyperglycemia, without allowing time for insulin action or food absorption.⁴¹ Based on this principle, individuals should be instructed to set alarms for hypoglycemia on their CGM device slightly higher than their actual threshold for hypoglycemia.⁵⁰

SELECTING APPROPRIATE CANDIDATES FOR CGM

The available data suggest that CGM use potentially benefits both T1D and T2D patients. Those on intensive insulin regimens, such as MDI or insulin pump therapy, require frequent SMBG and are at highest risk of hypoglycemia. For that reason, CGM is most useful in this particular patient population.⁷ The decision to initiate CGM is multifactorial and should be a shared decision between the patient and health care provider. Initiation of CGM requires motivation on the patient’s part to use CGM data appropriately to make medication dose adjustments while continuing frequent home glucose monitoring using fingersticks.Furthermore, patients should have an understanding of the basic principles of insulin therapy to be able to self-adjust doses.⁵⁶ In a small study of people with T1D, good coping skills, the ability to retrospectively analyze data, and adequate family involvement were all important factors for the effective use of CGM.⁵⁷

The frequency of CGM device use is another feature that can predict patients’ success with CGM. In the JDRF trial, the group that achieved significant A1C lowering (adults older than 25 years of age) had the greatest frequency of CGM use, with 83% of patients who wore the sensor at least 6 days a week while only 30% of those in the group with the least success in A1C lowering (15 to 24 years of age) wore the sensor at least 6 days a week.^52,56 Therefore, patient willingness to consistently use CGM should be assessed prior to initiation, with the cost of CGM devices being another important consideration.

In 2016, the AACE convened a public consensus conference to review available CGM data and develop strategies for overcoming barriers to GGM use and access. The group published a position statement advocating for expanded CGM coverage due to increasing evidence that such systems improve glycemic control, reduce hypoglycemia, and may reduce overall costs of diabetes management.⁵⁸ The ADA also provides the following specific recommendations related to CGM use:³⁷

• Sensor-augmented pump therapy may be considered for children, adolescents, and adults to improve glycemic control without an increase in hypoglycemia or severe hypoglycemia. Benefits correlate with adherence to ongoing use of the device.
• When prescribing CGM, robust diabetes education, training, and support are required for optimal CGM implementation and ongoing use.
• Real-time CGM should be considered in children and adolescents with T1D, whether using MDI or CSII, as an additional tool to help improve glucose control and reduce the risk of hypoglycemia. Benefits of CGM correlate with adherence to ongoing use of the device.
• When used properly, real-time CGM in conjunction with intensive insulin regimens is a useful tool to lower A1C in adults with T1D who are not meeting glycemic targets.
• Real-time CGM may be a useful tool in those with hypoglycemia unawareness and/or frequent hypoglycemic episodes.
• Real-time CGM should be used as close to daily as possible for maximal benefit.
• Real-time CGM may be used effectively to improve A1C levels and neonatal outcomes in pregnant women with T1D.
• Sensor-augmented pump therapy with automatic low-glucose suspend may be considered for adults with T1D at high risk of hypoglycemia to prevent episodes of hypoglycemia and reduce their severity.
• Intermittently scanned CGM use may be considered as a substitute for SMBG in adults with diabetes requirement frequent glucose testing.

As can be seen by reviewing the 2019 ADA recommendations for CGM use, CGM has an ever-expanding role in diabetes management.

COUNSELING TIPS FOR THE PHARMACIST

Pharmacists can play an integral role in educating patients regarding CGM use and interpretation. For patients to successfully use CGM devices, they should have a good understanding of CGM technology and the impacts of lifestyle, food, medications, and other variables on their BG levels.⁴¹ As medication experts, pharmacists can provide counseling regarding the onset, peak, and duration of diabetes medications.⁴⁵ Depending on the system used, pharmacists should discuss the need (or lack of need) for finger-stick monitoring. With systems now on the market that do not require fingerstick calibration, this is a potentially confusing point for patients. Also, people employing CGM devices should be encouraged to continuously review CGM retrospective data and share the information with their health care providers so consistent patterns may be evaluated and permanent lifestyle or medication changes may be made. A summary of key counseling points pharmacists can provide CGM users is available in Table 4.

FUTURE RESEARCH WITH PUMPS AND CGM DEVICES

Over the past several decades, diabetes research has focused on the development of automated, closed-loop insulin delivery systems, also known as the “artificial pancreas.” The closed-loop system consists of an insulin pump, a CGM apparatus, and advanced-control algorithm software embedded in a smartphone that is responsible for calculating rates of insulin delivery based on variables such as food, stress, and physical activity.⁵⁹ Traditionally, insulin pumps and CGM devices have operated independently of each other, relying on the user to set rates of insulin delivery based on CGM data. The first hospital-based closed-loop insulin delivery device became available in the 1970s. In the past decade, research has intensified to focus on development of individual, portable systems for home use. Availability of the Medtronic 670G system has brought the filed ever closer to a fully functional artificial pancreas.

There are several types of closed-loop systems currently available or under development. The FDA describes the following 3 categories of these systems: 1. Threshold Suspend Device systems, in which the delivery of insulin is suspended when glucose levels are below a specified threshold (Medtronic’s MiniMed 630G with SmartGuard is FDA-approved with this feature), 2. Control-to-Range (CTR) systems, in which insulin is only adjusted by the system if glucose levels are outside a prespecified range (users will still have to check BG levels and administer insulin), and 3. Control-to-Target (CTT) systems, in which the instrumentation aims to maintain glucose levels close to a target level. The FDA is helping to expedite the development of these systems by providing guidance to industry, prioritizing the review of research protocols, and shortening study review times.⁶⁰

SUMMARY

The technologic advancements of insulin pumps and CGM devices have significantly impacted the landscape of diabetes management for those who must have intensive insulin therapy. While insulin pumps and CGM instrumentation are not appropriate for all patients requiring intensive insulin therapy, the advances in these technologies and potential impacts on QoL make them attractive options for those who are appropriate candidates. While insulin pump therapy and CGM devices are usually initiated by diabetes specialists, pharmacists are likely to interact with patients who use these devices in community and institutional settings. As further research and development continue to create artificial pancreas technology, pharmacists should be familiar with current insulin pump and CGM devices, the advantages and disadvantages, and counseling tips to assist those using these devices in their practice.

REFERENCES

1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
2. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.
3. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-149.
4. Misso ML, Egberts KJ, Page M, et al. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010;(1):CD005103.
5. Labrousse-Lhermine F, Cazals L, Ruidavets J-B, Hanaire H. Long-term treatment combining continuous subcutaneous insulin infusion with oral hypoglycaemic agents is effective in type 2 diabetes. Diabetes Metab. 2007;33(4):253-260.
6. Pickup JC. Are insulin pumps underutilized in type 1 diabetes? Yes. Diabetes Care. 2006;29(6):1449-1452.
7. The American Diabetes Association. Standards of medical care in diabetes - 2016. Diabetes Care. 2016;39(Suppl 1):S1-S112.
8. Vincze G, Barner JC, Lopez D. Factors associated with adherence to self-monitoring of blood glucose among persons with diabetes. Diabetes Educ. 2004;30(1):112-125.
9. Gorst C, Kwok CS, Aslam S, et al. Long-term glycemic variability and risk of adverse outcomes: a systematic review and meta-analysis. Diabetes Care. 2015;38(12):2354-2369.
10. Jung HS. Clinical implications of glucose variability: chronic complications of diabetes. Endocrinol Metab (Seoul). 2015;30(2):167-174.
11. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2017.
12. Pickup JC, Keen H, Parsons JA, Alberti KG. Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. Br Med J. 1978;1(6107):204-207.
13. Tamborlane WV, Sherwin RS, Genel M, Felig P. Reduction to normal of plasma glucose in juvenile diabetes by subcutaneous administration of insulin with a portable infusion pump. N Engl J Med. 1979;300(11):573-578.
14. Pickup JC, Keen H, Viberti GC, et al. Continuous subcutaneous insulin infusion in the treatment of diabetes mellitus. Diabetes Care. 1980;3(2):290-300.
15. Mecklenburg RS, Benson JW Jr, Becker NM, et al. Clinical use of the insulin infusion pump in 100 patients with type I diabetes. N Engl J Med. 1982;307(9):513-518.
16. Reynolds LR. Reemergence of insulin pump therapy in the 1990s. South Med J. 2000;93(12):1157-1161.
17. Potti LG, Haines ST. Continuous subcutaneous insulin infusion therapy: a primer on insulin pumps. J Am Pharm Assoc (2003). 2009;49(1):e1-e13; quiz e14-e17.
18. Kaufman FR, ed. Medical Management of Type 1 Diabetes.6th ed. Alexandria, VA: American Diabetes Association; 2012.
19. Heise T, Meneghini LF. Insulin stacking versus therapeutic accumulation: understanding the differences. Endocr Pract. 2014;20(1):75-83.
20. Recently-approved devices. U.S. Food and Drug Administration. MiniMed 670G System. Available at: https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm600603.htm. Accessed April 16, 2019.
21. T:slim X2 Premarket FDA approval (Aug 25 2017). U.S. Food and Drug Administration. Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P140015S020. Accessed April 16, 2019.
22. Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ. 2002;324(7339):705.
23. Weissberg-Benchell J, Antisdel-Lomaglio J, Seshadri R. Insulin pump therapy: a meta-analysis. Diabetes Care. 2003;26(4):1079-1087.
24. Retnakaran R, Hochman J, DeVries JH, et al. Continuous subcutaneous insulin infusion versus multiple daily injections: The impact of baseline A1c. Diabetes Care. 2004;27(11):2590-2596.
25. Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med. 2008;25(7):765-774.
26. Slover RH, Welsh JB, Criego A, et al. Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study. Pediatr Diabetes. 2012;13(1):6-11.
27. Bruttomesso D, Crazzolara D, Maran A, et al. In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine. Diabet Med. 2008;25(3):326-332.
28. DeVries JH, Snoek FJ, Kostense PJ, et al. A randomized trial of continuous subcutaneous insulin infusion and intensive injection therapy in type 1 diabetes for patients with long-standing poor glycemic control. Diabetes Care. 2002;25(11):2074-2080.
29. Hoogma RP, Hammond PJ, Gomis R, et al. Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial. Diabet Med. 2006;23(2):141-147.
30. Roze S, Smith-Palmer J, Valentine W, et al. Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes: a systematic review. Diabet Med. 2015;32(11):1415-1424.
31. Monami M, Lamanna C, Marchionni N, Mannucci E. Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 2 diabetes: a meta-analysis. Exp Clin Endocrinol Diabetes. 2009;117(5):220-222.
32. Reznik Y, Cohen O, Aronson R, et al. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial. Lancet. 2014;384(9950):1265-1272.
33. Raskin P, Bode BW, Marks JB, et al. Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study. Diabetes Care. 2003;26(9):2598-2603.
34. Pickup J. Insulin pump therapy for type 1 diabetes mellitus. N Engl J Med. 2012;366(17):1616-1624.
35. Bruttomesso D, Costa S, Baritussio A. Continuous subcutaneous insulin infusion (CSII) 30 years later: still the best option for insulin therapy. Diabetes Metab Res Rev. 2009;25(2):99-111.
36. Grunberger G, Bailey TS, Cohen AJ, et al. Statement by the American Association of Clinical Endocrinologists Consensus Panel on insulin pump management. Endocr Pract. 2010;16(5):746-762.
37. American Diabetes Association. 7. Diabetes technology: Standards of Medial Care in Diabetes – 2019. Diabetes Care. 2019;42(Suppl. 1):S71-S80.
38. Boyd LC, Boyd ST. Insulin pump therapy training and management: an opportunity for community pharmacists. J Manag Care Pharm. 2008;14(8):790-794.
39. Umpierrez GE, Klonoff DC. Diabetes technology update: use of insulin pumps and continuous glucose monitoring in the hospital. Diabetes Care. 2018;41(8):1579-1589.
40. Clarke SF, Foster JR. A history of blood glucose meters and their role in self-monitoring of diabetes mellitus. Br J Biomed Sci. 2012;69(2):83-93.
41. Blevins TC, Bode BW, Garg SK, et al. Statement by the American Association of Clinical Endocrinologists Consensus Panel on continuous glucose monitoring. Endocr Pract. 2010;16(5):730-745.
42. Sato J, Hirose T, Watada H. Continuous glucose monitoring system: Is it really accurate, safe and clinically useful? J Diabetes Investig. 2012;3(3):225-230.
43. Klonoff DC. Continuous glucose monitoring: roadmap for 21st century diabetes therapy. Diabetes Care. 2005;28(5):1231-1239.
44. Messer L. CGM components, types, and wear. In: Chase HP, Messer L. Understanding InsulinPumps & Continuous Glucose Monitors. Denver, CO: Children’s Diabetes Foundation; 2007:103-108.
45. Block JM. Continuous glucose monitoring: changing diabetes behavior in real time and retrospectively. J Diabetes Sci Technol. 2008;2(3):484-489.
46. S. Food and Drug Administration (FDA) News Release. FDA permits marketing of first system of mobile medical apps for continuous glucose monitoring. January 23, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm431385.htm. Accessed April 25, 2019.
47. Dexcom G6 Approval Press Release (Mar 27 2018). U.S. Food and Drug Administration. Available at:
    https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm602870.htm. Accessed April 16, 2019.
48. FreeStyle Libre Approval Press Release (Sep 27 2017). U.S. Food and Drug Administration. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm577890.htm. Accessed April 16, 2019.
49. Poolsup N, Suksomboon N, Kyaw AM. Systematic review and meta-analysis of the effectiveness of continuous glucose monitoring (CGM) on glucose control in diabetes. Diabetol Metab Syndr. 2013;5:39.
50. Schwartz S, Scheiner G. The role of continuous glucose monitoring in the management of type-1 and type-2 diabetes. In: Evidence Based Management of Diabetes. Wynnewood, PA: Integrated Diabetes Services, LLC; 2012.
51. Gandhi GY, Kovalaske M, Kudva Y, et al. Efficacy of continuous glucose monitoring in improving glycemic control and reducing hypoglycemia: a systematic review and meta-analysis of randomized trials. J Diabetes Sci Technol. 2011;5(4):952-965.
52. Tamborlane WV, Beck RW, Bode BW, et al; Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008;359(14):1464-1476.
53. Chico A, Vidal-Rios P, Subirà M, Novials A. The continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with type 1 and type 2 diabetes but is not better than frequent capillary glucose measurements for improving metabolic control. Diabetes Care. 2003;26(4):1153-1157.
54. Battelino T, Phillip M, Bratina N, et al. Effect of continuous glucose monitoring on hypoglycemia in type 1 diabetes. Diabetes Care. 2011;34(4):795-800.
55. Bode B, Beck RW, Xing D, et al; Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Sustained benefit of continuous glucose monitoring on A1C, glucose profiles, and hypoglycemia in adults with type 1 diabetes. Diabetes Care. 2009;32(11):2047-2049.
56. Hirsch IB. Clinical review: realistic expectations and practical use of continuous glucose monitoring for the endocrinologist. J Clin Endocrinol Metab. 2009;94(7):2232-2238.
57. Ritholz MD, Atakov-Castillo A, Beste M, et al. Psychosocial factors associated with use of continuous glucose monitoring. Diabet Med. 2010;27(9):1060-1065.
58. Fonseca VA, Grunberger G, Anhalt H, et al. Continuous glucose monitoring: a consensus conference of the American Association of Clinical Endocrinologists and American College of Endocrinology. Endocr Pract. 2016;22(8):1008-1021.
59. Karoff P. Artificial pancreas system aimed at type 1 diabetes mellitus. Harvard Gazette. January 4, 2016. http://news.harvard.edu/gazette/story/2016/01/artificial-pancreas-system-aimed-at-type-1-diabetes-mellitus/. Accessed January 10, 2016.
60. S. Food and Drug Administration (FDA). The artificial pancreas device system. https://www.fda.gov/medicaldevices/productsandmedicalprocedures/homehealthandconsumer/consumerproducts/artificialpancreas/default.htm. Accessed April 25, 2019.

Back to Top