By: Emily Lammers, PharmD, MSLD; PGY2 Ambulatory Care/Academia Resident
Mentor: Lisa Cillessen, PharmD, BCACP; Clinical Assistant Professor, UMKC School of Pharmacy at MSU
Program Number: 2021-03-02
Approval Dates: April 7, 2021 to October 1, 2021
Approved Contact Hours: 1 hour
Diabetes mellitus is a chronic disease that affects over 34 million children and adults in the United States alone and 422 million people worldwide. This equates to a global presence of diabetes in people aged 18 years and older of 8.5%.1 In the United States specifically, 10.5% of the population are diagnosed with diabetes which equates to 1 in 10 Americans. Of the people in the United States diagnosed with diabetes, about 5% of the population, or 1.4 million, are diagnosed with Type 1 Diabetes Mellitus (T1DM) and 90- 95% are diagnosed with Type 2 Diabetes Mellitus (T2DM).2 These statistics show that diabetes mellitus is a common disease state that healthcare providers will encounter in their patients regardless of the environment in which they work.
Type 1 diabetes mellitus, which typically presents in adolescents and young adults, is characterized by the immune system destroying insulin producing cells in the pancreas causing the pancreatic beta cells completely stop producing insulin. This leaves the patient without an insulin supply. Insulin is responsible for binding to cells to allow glucose into the cells. If you think of a lock and key, insulin is the key that unlocks the cells and allows glucose to enter the cell. If the cells cannot take up glucose, the body cannot use this glucose for energy and the patient will be in a hyperglycemic state. Due to the lack of insulin in the body, patients with T1DM are indicated for insulin therapy as the treatment of choice. This patient population will require two to four injections per day of insulin. In combination with insulin injections, patients with T1DM need to monitor their blood sugar levels multiple times a day.3
Type 2 diabetes mellitus, which typically presents in older, overweight patients, is characterized by decreased beta cell function, insulin secretion and insulin sensitivity. The body still produces some insulin, but cells are not responding to the insulin to allow glucose into the cells. This is what leads to hyperglycemia in these patients and the diagnosis of T2DM. Patients with T2DM can be treated with both oral and injectable medications based on the severity of their disease. Some patients will not require injections, and some will require up to six injections per day. In combination with this, T2DM patients will need to monitor their blood sugars between one to four times daily depending on their treatment regimen and progression of disease.
Whether the patient has T1DM or T2DM, diabetes puts any patient at an increased risk of complications in the future. These complications can include cardiovascular disease, retinopathy, neuropathy, nephropathy, and others. One of the best ways to mitigate these risks is to have good management of the patient's diabetes and blood glucose levels. This includes staying at or below an A1c of 7% and maintaining blood sugars within the fasting (80-130 mg/dL) and postprandial (<180 mg/dL) goals as outlined by the American Diabetes Association. Based on the UKPDS 35 trial, every 1% reduction in A1c is correlated with a 21% decreased risk of diabetic complications.4 This trial and other evidence highlight the importance of maintaining proper control of blood glucose. One of the best ways for a patient to know the status of their blood sugars is to test, but many times patients are limited on the amount of times they can test in a day based on their insurance coverage and not wanting to continuously have finger sticks. This is an area where continuous glucose monitors (CGM) can come into play.
In 2016, the Endocrine Society appointed task force created recommendations and guidelines surrounding CGM use for patients with T1DM and T2DM. The task force recommends the use of CGMs in adult patients with T1DM who have A1c levels above target and who are willing and able to use these devices on a nearly daily basis. Secondly, the task force recommends CGM devices for adult patients with well-controlled T1DM who are willing and able to use these devices on a nearly daily basis. Thirdly, the task force recommends short-term, intermittent CGM use in adult patients with T2DM (not on prandial insulin) who have A1c levels 7% or higher and are willing and able to use the device. These recommendations indicate that CGMs place in therapy is growing and patients are benefiting from using CGMs.5
Continuous Glucose Monitors (CGM):
A continuous glucose monitor is a device a patient wears externally on either their abdomen or arm or is implanted. The device has a small sensor that will be inserted under the skin and automatically tracks a patient's interstitial blood glucose throughout the day and night. Interstitial fluid is part of the extracellular fluid between a patient’s cells and interstitial glucose values are determined by the rate of glucose diffusion from plasma to the interstitial fluid and the rate of glucose uptake by subcutaneous tissue cells.6 Interstitial glucose values can have a delay compared to blood glucose levels, so if a patient is experiencing signs of hypoglycemia, but the CGM device is not showing a hypoglycemic reading, the patient should verify with a blood glucose fingerstick.
CGMs have different components to them that include a sensor, transmitter, and receiver. The sensor is a small wire inserted subcutaneously and is responsible for measuring interstitial blood glucose levels every one to five minutes. The transmitter is a wireless component of the sensor that will transmit blood glucose levels to a receiver, reader, or application (app) on a smartphone.7 The sensor and transmitter are combined into a small, compact device that is attached externally to the body for most devices. There is one implantable CGM device on the market. Lastly, the receiver is a device that is separate from the sensor and transmitter. The receiver, which can be a small device or a compatible smart device, will display the transmitted data from the sensor. Different CGM devices are on the market and may have small differences from each other like where to place the sensor or the amount of time before each reading, but each device will have a sensor, transmitter, and receiver. Having the CGM device continuously track blood glucose levels allows patients and providers to see trends throughout the day and night and utilize these numbers to make medication or lifestyle changes.8
In recent trials completed in T1DM and T2DM patients, CGM have been shown to decrease hypoglycemic events. The IMPACT trial from 2016, showed patients with T1DM had a 38% reduction of time in hypoglycemia and a 40% nighttime reduction of hypoglycemia (<70 mg/dL)9. The REPLACE trial in 2017, showed that patients with T2DM had a 43% reduction of time in hypoglycemia and a 54% nighttime reduction of hypoglycemia (<70 mg/dL).10 This reduction provides a safer environment for patients and reduces worry for providers and patients regarding patients experiencing hypoglycemic events.
How many CGMs are on the market?
Pharmacists may have noticed that CGM devices have gained more popularity in recent years with the Freestyle Libre and Freestyle Libre 2 coming to market, but this was not the first CGM to be approved for use in patients with diabetes. Dexcom G6, Guardian Connect with the Guardian Sensor 3, and Senseonics Eversence are other continuous glucose monitors that are available to patients and have been since the early 2000’s.
The Dexcom G6 is the most current model that is available to patients and is equipped with a 10-day wearable sensor and transmitter. A patient will place the sensor and transmitter on their abdomen. The sensor and transmitter device are water-resistant and easy to insert with an auto-applicator. The Dexcom G6 transmitter wirelessly provides a glucose reading every five minutes, or up to 288 times per day to the receiver or a compatible smart device. These readings can be shared with up to ten others via the Dexcom Share feature. If a patient wishes to share data from their device with their healthcare provider, the information can be shared via the Dexcom Clarity software which allows providers to review CGM data at any time. The G6 is also equipped with an alert system for critically low blood sugars. The device monitors glucose trends and if glucose is trending downward, the device will alert a patient with a 20-minute advanced warning of a severe hypoglycemic event (<55 mg/dL). A patient will also have the option to set a “Low Alert” and “High Alert” for when their blood glucose readings are below or above target range. These alerts can be set, changed, or discontinued at any time by the patient. The alert for critically low blood sugars cannot be changed or stopped. The G6 is FDA permitted to make diabetes treatment decisions without confirmatory finger sticks or calibration needed, but if a patient is experiencing symptoms that are not in line with the readings they are receiving, fingerstick blood sugar should be taken to confirm.11
Guardian Connect and Guardian Sensor 3
The Guardian Connect CGM is powered by the Guardian Sensor 3, which can be worn up to seven days and is water-resistant for up to 30 minutes. The sensor measures interstitial blood glucose levels every five minutes. The transmitter will then automatically transfer these readings to the Guardian Connect app. The Guardian Connect app allows patients to set predictive high and low glucose values ranging from 10-60 minutes prior to predicted events happening. With the predictive alerts turned on to 30 minutes before a low, the Guardian Connect system had a 98.5% rate of detecting hypoglycemic events by evaluating if the patient’s glucose is trending downward. This system also allows patients to connect with their healthcare providers via the CareLink system platform. This platform enables providers virtual, remote monitoring of their patient’s glucose levels and trends. Another feature of the Guardian Connect system is the Sugar.IQ Diabetes Assistant cognitive app. This app uses IBM Watson analytics to identify patterns in diabetes data. The app continually analyzes how a patient’s glucose levels respond to their food intake, insulin dosages, and daily routines. This helps patients discover any hidden reasons for highs or low and gives a daily summary of glucose levels to allow patients to see how their blood sugar levels are trending.12
Eversence is the world’s first and only long-term, implantable CGM device. The sensor will be professionally placed by a healthcare provider every 90 days directly under the skin in a patient’s arm. The sensor is 3.5mm x 18.3mm. The sensor remains accurate if compressed and during exercise. The transmitter will sit right above the sensor on a patient’s arm and is removable, rechargeable, and water-resistant up to 30 minutes. A benefit of the transmitter being removable is patients can remove the device for a special occasion and they will not waste a sensor because the sensor and transmitter are not attached. The transmitter will send data to a patient’s smart device every five minutes via Bluetooth. The transmitter will provide on-the-body vibration alerts when a patient’s blood glucose is too high or too low in addition to alerts the patient can see and hear. Eversence is the only CGM on the market that includes vibration alerts. Blood glucose levels are automatically sent to a patient’s smart device from the transmitter, the patient’s smart device will track the real-time glucose measurements with no need for a different receiver. The patient can also track exercise and meals to see them on the graph and aid in identifying trends. The data sent to the smart device can be shared with up to five people of the patient’s choosing and could include members of the healthcare team.13
Freestyle Libre 14-day
Freestyle Libre is a 14-day sensor that a patient wears on the upper part of the back of their arm. The sensor filament is less than 0.4mm thick and is water- resistant. The receiver is a separate device that patients can use to scan the sensor to obtain their glucose readings. A patient can also use their smart device with the LibreLink app if preferred. Patients may scan the transmitter as often as they want while they are wearing the sensor and a new reading is available every minute to view with the system storing glucose readings every 15 minutes. It is required that patients do scan the sensor at least once every eight hours or data will be lost for that time period. Each scan will show the patient’s current blood sugar reading, direction sugars are trending, and a trend graph showing the last eight hours of glucose history. The reader will hold up to 90 days of glucose history including daily patterns, time in target, low glucose levels, and 7, 14 and 30-day averages. This data is available to be shared with up to 20 people like family members or healthcare providers via the LibreLinkUp app. Freestyle Libre 2, which was approved Summer 2020, is the most recent version of the Freestyle Libre devices. The Libre 2 has all the features of the previous versions and includes alerts for high and low blood sugars for the patient. Along with that, the Libre 2 has an online portal called LibreView that can be accessed by patients and healthcare providers to share CGM data. The Libre 2 is not currently approved to be used with the LibreLink app, so patients will need to have the receiver accessible to scan the sensor at least once every 8 hours. The receiver can double as a glucose meter if the patient needs to perform a fingerstick blood sugar check.14
Comparison of Continuous Glucose Monitors
How do I interpret the numbers?
The glucose readings, trend lines, averages, and alerts from a continuous glucose monitor can seem daunting as a healthcare provider trying to figure out what to do with all the information. From a figure used in an article written by Dr. Bergenstal, this article will go through how to interpret all the information from a CGM report.
This figure is from a FreeStyle Libre device, but many of the CGMs on the market will produce similar data to what is in the image above. The average glucose has a high correlation with A1c, but not as much with glycemic variability or hypoglycemia. If a healthcare provider were to only utilize this number when making a treatment decision it does not give much information around glucose patterns. The glucose management index is a substitution for estimated A1c. This number is calculated from the mean CGM glucose over a specified period of time. The next item to take a look at is the time in range (TIR). This graph shows the time a patient is in target range, above and below. As healthcare providers, we want to try to maximize our patient’s time in range and minimize the time above and below. The image above shows the TIR as a percentage, but some data will show it in minutes or hours in range per day averaged over the allotted time period. TIR will automatically set up to 70-180 mg/dL, but if a patient or provider wants to alter the target levels that is available to do. The time in hypo- and hyperglycemia have specified values and then beyond that will have critical values. These are shown above with <70 mg/dL considered below target range, but then it also specifies what percentage of that time the patient spent <54 mg/dL. These values can be extremely useful for healthcare providers to identify how often a patient is below or above goal. Using this information paired with the graph on time to see when exactly the patient is experiencing the time above or below can aid the provider in making very informed, specific medication regimen changes. The coefficient of variation (CV) is a value that is used to mark glucose variability. It has been studied that a CV of <36% represents low glucose variability and a stable glucose profile and ≥ 36% is vice versa. Standard deviation (SD) highly correlates with mean glucose and A1c. If the SD is less than the mean glucose divided by three, a provider can assume low glucose variability and a stable glucose profile. Lastly, the ambulatory glucose profile with the dark blue line being the median with 50% of glucose levels above and 50% below. The dark blue shading is indicative of 50% of all glucose readings and the light blue is 80% of readings for the specified time. This graph is a visual that healthcare providers can quickly look at to identify how often and at what times a patient is in target range. It is also a great tool to use to identify what times a day a patient is at risk for a hypoglycemic event and can alter medication regimens to mitigate chances of hypoglycemia.15
A CGM report may seem daunting at first but breaking down each part and understanding what it means in the big picture could be helpful. While this article discussed specifically FreeStyle Libre, this information is transferable to any CGM report that a provider may be interpreting with some small differences present.
What monitor is right for my patient?
Insurance companies play a huge part in identifying which monitor may be right for a patient. Insurance companies issue preferred drug lists that indicate which medications and devices are preferred for that specific insurance company. This does not mean that non-preferred medications will not be covered to some extent but may have a higher copay or require a prior authorization. It is more common that insurance companies will provide coverage for continuous glucose monitor devices for patients with T1DM as these patients typically require more daily finger sticks and are treated solely with insulin which may put them at an increased risk for hypoglycemic episodes.
Each company with a CGM on the market will also have a team available for patients or providers to help with coverage. The pharmaceutical companies want patients using their products, so they offer many resources to help with the processing of paperwork and finding coverage opportunities for patients. Below is a list of insurance coverage and criteria that must be met for common insurances that pharmacists in Missouri may encounter. Commercial insurance companies have similar criteria, so only one has been listed below.
Missouri Medicaid covers Dexcom G6 for patients who meet certain criteria including:16
Blue Cross Blue Shield of Missouri
Blue Cross Blue Shield of Missouri covers Freestyle Libre 14 and Dexcom G6 at a tier 2 and ST. The step therapy qualifications are listed below for FreeStyle Libre 14 Day and similar steps are required for Dexcom G6:17
The Medicare National Coverage Determinations Manual has released the following information regarding coverage of a CGM for patients with Medicare insurance.18
Considering the different eligibility criteria for commonly seen insurance plans in Missouri, it can be hard for patients to gain approval for continuous glucose monitoring devices. There is always the option for patients to pay out of pocket, but that can be a considerable expense for patients. Continuous glucose monitors are great devices that have proven to decrease times in hypoglycemia and overnight hypoglycemia for patients. There is also the benefit of information sharing with friends, family, and the healthcare team. For healthcare providers, it makes our decision-making process more exact when we can identify trends in glucose over time instead of a moment in time blood sugar. With all those benefits being mentioned, cost and eligibility are the largest barriers. To increase accessibility to patients, there needs to be a reduction in cost or loosened eligibility criteria for patients with T1DM and T2DM.