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MP 1.01.20

Continuous or Intermittent Monitoring of Glucose in Interstitial Fluid


Medical Policy    
Section
Durable Medical Equipment
 
Original Policy Date
8/18/00

Last Review Status/Date
Reviewed with literature search/3:2013

Issue
3:2013
 

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Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

 


Description

Tight glucose control in patients with diabetes has been associated with improved outcomes. Several devices are available to measure glucose levels automatically and frequently (e.g., every 5 to 10 minutes). The devices measure glucose in the interstitial fluid and are approved as adjuncts to traditional self-monitoring of blood glucose levels.

Background

The advent of blood glucose monitors for use by patients in the home over 20 years ago revolutionized the management of diabetes. Using fingersticks, patients could monitor their blood glucose level both to determine the adequacy of hyperglycemia control and to evaluate hypoglycemic episodes. Tight diabetic control, defined as a strategy involving frequent glucose checks and a target HgA1c in the range of 7%, is now considered standard of care for diabetic patients. Randomized controlled trials (RCTs) of tight control have demonstrated benefits for type I diabetics in decreasing microvascular complications. The impact of tight control on type II diabetic patients and on macrovascular complications such as stroke or myocardial infarction (MI) is less certain.

However, tight glucose control requires multiple measurements of blood glucose each day (i.e., before meals and at bedtime), a commitment that some patients may be unwilling or unable to meet. In addition, the goal of tight glucose control has to be balanced with an associated risk of hypoglycemia. An additional limitation of periodic self-measurements of blood glucose is that glucose values are seen in isolation, and trends in glucose levels are undetected. For example, while a diabetic patient’s fasting blood glucose level might be within normal values, hyperglycemia might be undetected postprandially, leading to elevated hemoglobin A1c values.

Recently, measurements of glucose in interstitial fluid have been developed as a technique of automatically measuring glucose values throughout the day, producing data that show the trends in glucose measurements, in contrast to the isolated glucose measurements of the traditional blood glucose measurements. Although devices measure glucose in interstitial fluid on a periodic rather than a continuous basis, this type types of monitoring is referred to as continuous glucose monitoring (CGM).

Several devices have received U.S. Food and Drug Administration (FDA) approval. The first two approved devices were the Continuous Glucose Monitoring System (CGMS®) (MiniMed), which uses an implanted temporary sensor in the subcutaneous tissues, and the GlucoWatch G2® Biographer, an external device worn like a wristwatch that measures glucose in interstitial fluid extracted through the skin with an electric current (referred to as reverse iontophoresis).

Additional devices that have subsequently been approved include those for pediatric use and those with more advanced software, more frequent measurements of glucose levels, more sophisticated alarm systems, etc. Devices initially measured interstitial glucose every 5 to 10 minutes and, with currently available devices the time intervals at which interstitial glucose is measured ranges from every 1-2 minutes to 5 minutes. While continuous glucose monitors potentially eliminate or decrease the number of required daily fingersticks, it should be noted that, according to the FDA labeling, monitors are not intended to be an alternative to traditional self-monitoring of blood glucose levels but rather provide adjunct monitoring, supplying additional information on glucose trends that are not available from self-monitoring. In addition, it is important to note that devices may be used intermittently, e.g., time periods of 72 hours, or on a long-term basis.

In addition to stand-alone continuous glucose monitors, several insulin pump systems have included a built-in CGM. This policy addresses continuous glucose monitoring devices, not the insulin pump portion of these systems. Also, under development is what is known as an artificial pancreas or artificial pancreas device system (APDS). The proposed artificial pancreas is a series of devices e.g., a CGM, blood glucose device and an insulin pump, plus a computer algorithm that communicates with all of the devices. The goal of the APDS is to automatically monitor glucose levels and adjust insulin levels. These systems are also called closed-loop systems or autonomous systems for glucose control. One technology associated with artificial pancreas development is a “low glucose suspend (LGS)” feature included with an insulin pump. The LGS feature is designed to suspend insulin delivery when plasma glucose levels fall below a pre-specified threshold.

Regulatory Status

Several continuous glucose monitoring systems have been approved by the FDA through the premarket approval process:

  • The Continuous Glucose Monitoring System (CGMS®) (MiniMed) in 1999 (approved for 3-day use in a physician's office).
  • The GlucoWatch G2® Biographer in 2001. Of note, neither the GlucoWatch nor the autosensors have been available after July 31, 2008.
  • The Guardian®-RT (Real-Time) CGMS (Medtronic, MiniMed) in July 2005. (MiniMed was purchased by Medtronic).
  • The DexCom® STS CGMS system (DexCom) was approved by the FDA in March 2006.
  • The Paradigm® REAL-Time System (Medtronic, MiniMed) was approved by the FDA in 2006. This system integrates a continuous glucose monitor with a Paradigm insulin pump. The second generation integrated system is called the MiniMed Paradigm Revel System.
  • The FreeStyle Navigator® CGM System (Abbott) was approved in March 2008.
  • The OmniPod® Insulin Management System (Insulet Corporation), integrating the Freestyle Navigator CGM system with the Pod insulin pump, was approved in December 2011.

No artificial pancreas device systems have received U.S. Food and Drug Administration (FDA) approval or clearance. However, the FDA is taking an active role in the development of an artificial pancreas device system, including providing clear guidance to industry on performance and safety standards and sponsoring public forums. In addition, “low glucose suspend” technology has not received FDA approval.

 


Policy

Intermittent monitoring, i.e., 72 hours, of glucose levels in interstitial fluid may be considered medically necessary in patients with type 1 diabetes mellitus whose diabetes is poorly controlled despite current use of best practices (see Policy Guidelines). Poorly controlled type 1 diabetes mellitus includes the following clinical situations: unexplained hypoglycemic episodes, hypoglycemic unawareness, suspected postprandial hyperglycemia, and recurrent diabetic ketoacidosis.

Intermittent monitoring of glucose levels in interstitial fluid may also be considered medically necessary in patients with type I diabetes prior to insulin pump initiation to determine basal insulin levels.

Continuous, i.e., long-term, monitoring of glucose levels in interstitial fluid, including real-time monitoring, as a technique of diabetic monitoring, may be considered medically necessary when the following situations occur despite use of best practices:

Patients with type I diabetes who have recurrent, unexplained, severe (generally blood glucose levels less than 50 mg/dL) hypoglycemia which puts the patient or others at risk; or Patients with type I diabetes who are pregnant whose diabetes is poorly controlled. Poorly controlled type I diabetes includes unexplained hypoglycemic episodes, hypoglycemic unawareness, suspected postprandial hyperglycemia, and recurrent diabetic ketoacidosis.

Other uses of continuous monitoring of glucose levels in interstitial fluid as a technique of diabetic monitoring are considered investigational.

Use of an artificial pancreas system, including but not limited to closed-loop monitoring devices with low-glucose suspend (LGS) features, are considered investigational.


Policy Guidelines

Several insulin pump systems (e.g., Omnipod Insulin Management System, Paradigm REAL-Time System) have a built-in continuous glucose monitor (CGM). This policy is evaluating the CGM-device only; the policy does not evaluate insulin pumps. In the case of insulin pumps systems with a built-in CGM and a low glucose suspend (LGS) feature, the CGM device and the low glucose suspend feature are evaluated in the policy, not the insulin pump.

Best practices in diabetes control for patients with diabetes mellitus include compliance with a regimen of 4 or more fingersticks each day and use of an insulin pump. During pregnancy, 3 or more insulin injections daily could also be considered best practice for patients not on an insulin pump prior to the pregnancy. Prior use of an intermittent (72-hour) glucose monitor would be considered a part of best practices for those considering use of a continuous glucose monitor.

Women with type 1 diabetes mellitus taking insulin who are pregnant or about to become pregnant with poorly controlled diabetes are another subset of patients to whom the policy statement on intermittent monitoring may apply.

Intermittent monitoring is generally conducted in 72-hour periods. It may be repeated at a subsequent time depending on the patient’s level of diabetes control.

The strongest evidence exists for use of CGM devices in patients age 25 and older. However, age may be a proxy for motivation and good control of disease, so it is also reasonable to select patients based on their ability to self-manage their disease, rather than age.

In 2009, the language of the CPT codes that specifically describe monitoring of glucose levels in the interstitial fluid using implanted devices was revised to state that the devices are used for a minimum of 72 hours:

95250: Ambulatory continuous glucose monitoring of interstitial tissue fluid via a subcutaneous sensor for a minimum of 72 hours; hook-up, calibration of monitor, patient training, removal of sensor, and printout of recording

95251 ;interpretation and report

CPT code 99091 might also be used for this monitoring:

99091: Collection and interpretation of physiologic data (e.g., ECG, blood pressure, glucose monitoring) digitally stored and/or transmitted by the patient and/or caregiver to the physician or other qualified healthcare professional, requiring a minimum of 30 minutes of time.

For 2008, HCPCS codes were added specifically for continuous glucose monitoring systems:

A9276 Sensor; invasive (e.g., subcutaneous), disposable, for use with interstitial continuous glucose monitoring system, one unit=1 day supply

A9277 Transmitter; external, for use with interstitial continuous glucose monitoring system

A9278 Receiver (monitor); external, for use with interstitial continuous glucose monitoring system

 

Benefit Application

BlueCard/National Account Issues

State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-approved devices may be assessed on the basis of their medical necessity.

State mandates regarding coverage of diabetic supplies may apply; however, some state mandates may only apply to those supplies that are no longer considered investigational.

 


Rationale

This policy was originally created in 2000 and was updated regularly with searches of the MEDLINE database. A TEC Assessment was published in 2003. (1) The most recent literature search was performed for the period January 2012 through February 6, 2013. Following is a summary of the key literature to date:

Continuous glucose monitoring systems

Type 1 diabetes

In 2007, Wilson and colleagues published data from the Diabetes Research in Children Network (DirecNet) on the accuracy and precision of the FreeStyle Navigator CGM System in 30 children with type 1 diabetes (mean age 11.2 years). (2) The Navigator glucose values were compared with reference serum glucose values of blood samples obtained in an inpatient clinical research center and measured in a central laboratory and in an outpatient setting with a FreeStyle meter. Median absolute difference (AD) and median relative absolute difference (RAD) were computed for sensor-reference and sensor-sensor pairs. The median AD and RAD were 17 mg/dL and 12%, respectively, for 1,811 inpatient sensor-reference pairs and 20 mg/dL and 14%, respectively, for 8,639 outpatient pairs. The median RAD between 2 simultaneous Navigator measurements (n=1,971) was 13%. Ninety-one percent of sensors in the inpatient setting and 81% of sensors in the outpatient setting had a median RAD of 20% or less.

Most of the discussion below focuses on the clinical utility of continuous glucose monitoring systems (CGMS). That is, their ability to provide either additional information on glucose levels, leading to improved glucose control or to improve the morbidity/mortality associated with clinically significant severe and acute hypoglycemic or hyperglycemic events. Because diabetic control encompasses numerous variables including the diabetic regimen and patient self-management, randomized controlled trials (RCTs) are important to isolate the contribution of interstitial glucose measurements to the overall diabetic management.

Several meta-analyses of RCTs have been published; they have focused on slightly different populations e.g. age and/or type of diabetes, and different study designs e.g. by length of follow-up. In 2011, Gandhi and colleagues conducted a systematic review of RCTs evaluating continuous glucose monitoring (CGM) that included adults or children and individuals with type 1 or type 2 diabetes. (3) To be eligible, studies needed to have at least 8 weeks follow-up and be conducted in the outpatient setting. Studies of both real-time and non-real-time CGM devices were included; control groups needed to utilize self-monitored blood glucose (SMBG). Nineteen trials met their eligibility criteria and provided data for meta-analysis. Mean baseline HbA1c was at least 7.0% in all studies but included one in which the mean baseline HbA1c was 6.4%. Overall, compared with self-monitoring of blood glucose, CGM was associated with a statistically significant reduction in mean HbA1c (weighted mean difference [WMD]: -0.27%, 95% confidence interval [CI]: -0.44 to -0.10%). When stratified by age and type of diabetes, there was a statistically significant reduction in HbA1c in adults with type 1 diabetes and adults with type 2 diabetes, but not in studies of children and adolescents with type 1 diabetes.

Another 2011 meta-analysis of RCTs on CGM included trials conducted in adults and children with type 1 diabetes who were on an intensive insulin regimen (studies of type 2 diabetes were not included). (4) This meta-analysis required a minimum of 12 weeks of follow-up in the studies (as compared to at least 8 weeks in the Gandhi meta-analysis). Studies compared CGM to SMBG; there was no restriction related to type of CGM device, but the CGM readings had to be used to adjust insulin dose or modify diet. A total of 14 RCTs met eligibility criteria. In a pooled analysis, there was a statistically significant reduction in HbA1c with CGM compared to SMBG, WMD: -0.26%, 95% CI: -0.34 to -0.19%. In a sub-group analysis by age, there were significant reductions in HbA1c with CGM in studies of adults (n=5), WMD: -0.33 (95% CI: -0.46 to -0.20) and in studies with children and/or adolescents (n=8), WMD: -0.25, 95% CI: -0.43 to -0.08. Two 2012 meta-analyses evaluating the efficacy of CGM in patients with type 1 diabetes had similar findings: overall, use of CGM to result in significantly greater reductions in HbA1c compared to SMBG. (5, 6)

Representative RCTs are described below:

In 2008, the Juvenile Diabetes Research Foundation (JDRF) published results of a study that randomly assigned 322 adults and children with type I diabetes to continuous glucose monitoring or self-(home) monitoring. (7) With HbA1c as the primary outcome measure, there was a significant difference among patients 25 years of age or older that favored continuous monitoring (mean HbA1c difference: 0.53%), while the difference between groups was not statistically significant for those ages 15 to 24 years or 8 to 14 years. The population in this study had relatively well-controlled diabetes in that entry criterion was glycated Hb of 7% to 10%, but approximately 70% had levels between 7% and 8%; in addition, more than 70% of patients were using an insulin pump. No significant differences were noted in rates of hypoglycemic events, but the study was likely not sufficiently large to detect potential differences. The authors also reported that monitor use was greatest in those patients ages 25 or older, the group in which 83% of patients used the monitor 6 or more days per week. The investigators also conducted a non-blinded single-arm 6-month extension to the randomized trial in which patients in the control group were offered a CGM device. (8) A total of 214 of 219 (98%) in the control group participated in the extension. This included 80 (37%) who were at least 25-years old, 73 (34%) who were 15-24-years old, and 61 (29%) who were 8-14-years old. The mean HbA1c level at the time of initiation of CGM use was 7.4 +/- 0.7%. Patients were instructed to use the device on a daily basis. Among the 154 patients with baseline A1c at least 7%, there was a significant decrease in A1c 6 months after initiating device use in the older age group (mean change in A1C: -0.4% +/- 0.5%, p<0.001). HbA1c did not decrease significantly in the 15-24-year olds (0.01 +/- 0.7%, p=0.95) or in the 8-14-year olds (0.02 +/- 0.7%, p=0.85). Greater decrease in HbA1c was associated with more frequent use of the CGM device (p=0.001, adjusted for age group). Frequency of device used tended to decrease over time, with less of a decrease in the older age group. At month 6, median use of CGM devices was 6.5 days per week among the older age group, 3.3 days among the 15-24-year olds, and 3.7 days per week among the children. During the 6-month extension, the rate of severe hypoglycemic events was 15 per 100 person-years of follow-up.

An additional randomized trial by the Juvenile Diabetes Research Foundation, published in 2009, studied the potential benefits of CGM in the management of adults and children with well-controlled type 1 diabetes. (9) In this study, 129 adults and children with intensively treated type 1 diabetes (age range 8-69 years) and HbA1c less than 7.0% were randomly assigned to either continuous or standard glucose monitoring for 26 weeks. The main study outcomes were time with glucose level at or below 70 mg/dL, HbA1c level, and severe hypoglycemic events. At 26 weeks, biochemical hypoglycemia (at or below 70 mg/dL) was less frequent in the CGM group than in the control group (median 54 vs. 91 min/day, respectively), but the difference was not statistically significant (p=0.16). Time out of range (70 or less or greater than 180 mg/dL) was significantly lower in the CGM group than in the control group (377 vs. 491 min/day, respectively, p=0.003). There was a significant treatment group difference favoring the CGM group in mean HbA1c at 26 weeks adjusted for baseline values. One or more severe hypoglycemic events occurred in 10 and 11% of the 2 groups, respectively (p not significant). The authors concluded that the weight of evidence suggests that CGM is beneficial for individuals with type 1 diabetes who have already achieved excellent control with HbA1c of less than 7.0%. This is a relatively small study. In addition, the clinical significance of some of these findings is not certain. Some of the patients in this group would likely meet policy statements for use of CGM.

The MITRE trial, published by Newman and colleagues in 2009, was conducted to evaluate whether the additional information provided by use of minimally invasive glucose monitors resulted in improved glucose control in patients with poorly controlled insulin-requiring diabetes. (10) This was a 4-arm RCT conducted at secondary care diabetes clinics in 4 hospitals in England. In this study, 404 people aged older than 18 years, with insulin-treated diabetes mellitus (types 1 or 2) for at least 6 months, who were receiving 2 or more injections of insulin daily, were eligible. The majority of participants, 57%, had type 1 diabetes, 41% had type 2 diabetes and 2% were classified as “other.” Participants had 2 HbA1c values of at least 7.5% in the 15 months prior to entry and were randomized to 1 of 4 groups. Two groups received minimally invasive glucose monitoring devices (GlucoWatch Biographer or MiniMed Continuous Glucose Monitoring System, CGMS). Intermittent CGM was used i.e. monitoring was performed over several days at various points in the study. These groups were compared with an attention control group (standard treatment with nurse feedback sessions at the same frequency as those in the device groups) and a standard control group (reflecting common practice in the clinical management of diabetes). Change in HbA1c from baseline to 3, 6, 12, and 18 months was the primary indicator of short- to long-term efficacy in this study. At 18 months, all groups demonstrated a decline in HbA1c levels from baseline. Mean percentage changes in HbA1c were -1.4 for the GlucoWatch group, -4.2 for the CGMS group, -5.1 for the attention control group, and -4.9 for the standard care control group. In the intent-to-treat (ITT) analysis, no significant differences were found between any of the groups at any of the assessment times. There was no evidence that the additional information provided by the devices resulted in any change in the number or nature of treatment recommendations offered by the nurses. Use and acceptability indicated a decline in use of both devices, which was most marked in the GlucoWatch group by 18 months (20% still using GlucoWatch vs. 57% still using the CGMS). In this study of unselected patients, use of continuous glucose monitors (CGMS on an intermittent basis) did not lead to improved clinical outcomes.

In 2011, Mauras and colleagues published an analysis from the Diabetes Research in Children Network (DirecNet) Study Group that evaluated CGM in the management of young children aged 4 to less than 10 years with type 1 diabetes (11) A total of 146 children (mean age 7.5 years) were randomized to CGM or usual care. At baseline, 30 children (42%) had an HbA1c of at least 8%. The primary outcome was clinical success as defined as reduction in HbA1c by at least 0.5% without the occurrence of severe hypoglycemia at 26 weeks. Clinical success was attained by 19% in the CGM group and 28% in the usual care group; p=0.17. Mean change in HbA1c, a secondary outcome, did not differ significantly between groups (-0.1 in each group, p=0.79).

Type 2 diabetes

The 2011 meta-analysis by Gandhi and colleagues, discussed above, included studies of type 1 and type 2 diabetes. (3) Three RCTs included inpatients with type 2 diabetes (one of these included patients with either type of diabetes). There was a mixture of patients with type 2 diabetes who did and did not require insulin. In a meta-analysis of the 3 trials, there was a statistically significant reduction in HbA1C with CGM compared to SMBG in adults with type 2 diabetes (WMD: -0.70, 95% CI: -1.14 to -0.27).

In addition, an industry-sponsored RCT was identified that evaluated intermittent use of a CGM device in 100 patients with type 2 diabetes who were not on prandial insulin; findings were first published in 2011. (12, 13) Eligible participants were 18 or older, had type 2 diabetes for at least 3 months, and had an initial HbA1c of at least 7% but not more than 12%. The study compared real-time continuous monitoring with the DexCom device used for four 2-week cycles (2 weeks on/ 1 week off) to self-monitoring of blood glucose (SMBG). The primary efficacy outcome was mean change in HbA1c. The mean decline from baseline in HbA1c in the CGM versus the SMBG group was 1.0% versus 0.5% at 12 weeks, 1.2% versus 0.5% at 24 weeks, 0.8% versus 0.5% at 38 weeks, and 0.8% versus 0.2% at 1 year, respectively. Over the course of the study, the reduction in HbA1c was significantly greater than in the SMBG group (p=0.04). After adjusting for potential confounding variables including age, sex, baseline therapy, and whether the individual started taking insulin during the study, the difference between groups over time remained statistically significant (p<0.0001).

Another randomized trial is underway that is evaluating CGM for people with type 2 diabetes who have an HbA1c of at least 7% (see section on Ongoing Clinical Trials, below).

Pregnant women with diabetes

It is believed that more intensive glucose monitoring may be beneficial for pregnant patients, in whom hypo- and hyperglycemia are of greater concern. In 2013, an RCT was published evaluating CGM for use by women with diabetes during pregnancy. (14) In this study, Secher and colleagues in Denmark randomized 154 women to real-time CGM in addition to routine pregnancy care (n=79) or routine pregnancy care alone (n=75). There were 123 women with type 1 diabetes and 31 with type 2 diabetes. Patients in the CGM group were instructed to use the CGM device for 6 days prior to each of 5 study visits and were encouraged to use the devices continuously. Participants in both groups were instructed to perform 8 daily self-monitored plasma glucose measurements for 6 days before each visit. Baseline mean HbA1c was 6.6% in the CGM group and 6.8% in the routine care group. The 154 pregnancies resulted in 149 live births and 5 miscarriages. The prevalence of large-for-gestational age infants (at least 90th percentile), the primary study outcome, was 45% in the CGM group and 34% in the routine care group. The difference between groups was not statistically significant, p=0.19. In addition, no statistically significant differences were found between groups for secondary outcomes, including the prevalence of preterm delivery and the prevalence of severe neonatal hypoglycemia. Women in this study had low baseline HbA1c, which might help explain the lack of impact of CGM on outcomes. Other factors potentially contributing to the negative findings include the intensive SMBG routine in both groups and the relatively low compliance rate (64%) in the CGM group with the instruction of use the CGM devices for 6 days before each of 5 study visits.

Another RCT with a similar study design, known as the GlucoMOMs trial, is underway in the Netherlands; the study protocol was published in 2012. (15) The study is including pregnant women with type 1 or 2 diabetes who are on insulin therapy, or women with gestational diabetes who require insulin before 30 weeks’ gestation. Women will be randomized to CGM or usual care groups. The primary outcome measure is the rate of large-for-gestational age infants (above the 90th percentile). The estimated sample size is 150 women per group.

Other diabetic subgroups

CGM has been proposed for specific diabetic subgroups such as patients with poor diabetic control, as evidenced by recurrent hypoglycemia, hypoglycemia unawareness, postprandial hyperglycemia, and/or recurrent diabetic ketoacidosis. For these groups, CGM provides different types of information than single glucose measurements, such as trends in glucose and rates of change. There is only anecdotal evidence for the efficacy of this approach; there is no high-quality evidence available to evaluate the impact of this approach on health outcomes.

Continuous glucose monitoring systems integrated with an insulin pump

Recent advances in technology now allow linkage between the CGM device and an insulin pump. In a randomized study of 132 adults and children from France reported in 2009, Raccah and colleagues reported improved HbA1c levels (change in A1c of 0.96% vs. 0.55%, respectively) in patients who were fully protocol compliant for use of an insulin pump integrated with CGMS compared to those using a pump with standard glucose self-monitoring. (16) In 2012, Battelino and colleagues published findings of a multicenter crossover study conducted in several European countries that included 153 children and adults with type 1 diabetes.(17) The study used the MiniMed Paradigm REAL-Time system, which integrates a CGM device and an insulin pump system. Patients were randomized to use of the system for 6 months with the sensor on and 6 months with the sensor off, in random order, with a washout period of 4 months between interventions. Baseline HbA1c ranged from 7.5-9.5%. After treatment, mean HbA1c was 8.04% in the sensor on arm and 8.47% in the sensor off arm. The mean difference in HbA1c between groups was -0.43% (95% CI: -0.32% to -0.55%), p<0.001. Neither of the above trials was blinded, and neither compared continuous to intermittent use of the CGM.

Artificial pancreas device systems (APDS), including low glucose suspend (LGS) technology

Artificial pancreas systems, as currently in development, consist of a series of devices including a CGM, insulin pump and blood glucose device, controlled by a computer algorithm to automatically monitor glucose levels and adjust insulin doses. As of February 2013, there are no FDA-approved artificial pancreas devices.

One published study has used a CGM device integrated with Paradigm® VEO™ insulin pump and evaluated a feature to suspend insulin delivery when glucose levels fall below a pre-specified threshold, known as a “low glucose suspend (LGS)” feature. The study, called the Automation to Simulate Pancreatic Insulin Response (ASPIRE) was published in 2012 by Garg and colleagues. (18) It was a randomized, crossover trial that included 50 patients with type 1 diabetes who had at least 3 months’ experience with an insulin pump system. After a 2-week run-in period to verify and optimize basal rates, patients underwent 2 in-clinic exercise sessions to induce hypoglycemia. The LGS feature on the insulin pump was turned on in one session and off in the other session, in random order. When on, the LGS feature was set to suspend insulin delivery for 2 hours when levels reached 70 mg/dL or less. The goal of the study was to evaluate whether the severity and duration of hypoglycemia was reduced when the LGS feature was used. The study protocol called for patients to start exercise with a glucose level of 100-140 mg/dL, and to use a treadmill or stationary bicycle until their plasma glucose level was 85 mg/dL or less. The study outcome, duration of hypoglycemia, was defined as the period of time glucose values were lower than 70 mg/dL and above 50 mg/dL, and hypoglycemia severity was defined as the lowest observed glucose value. A successful session was defined as an observation period of 3-4 hours and with glucose levels above 50 mg/dL. Patients who did not attain success could repeat the experiment up to 3 times.

The 50 patients attempted 134 exercise sessions; 98 of these were successful. Duration of hypoglycemia was significantly less during the LGS-on sessions (mean: 138.5 minutes, standard deviation (SD): 68 minutes) than the LGS-off sessions (mean: 170.7 minutes, SD: 91): p=0.006. Hypoglycemia severity was significantly lower in the LGS-on group. The mean lowest glucose level was 59.5 mg/dL (SD: 72) in the LGS-on group and 57.6 mg/dL (SD: 5.7) in the LGS-off group, p=0.015. The Garg study evaluated the LGS feature in a research setting and over a short time period. Another arm of the ASPIRE study evaluating the LGS feature in the outpatient setting over 5 months is underway (see section below on ongoing clinical trials).

A second RCT evaluating a low-glucose suspend device was performed by the Diabetes Wireless Artificial Pancreas Consortium, using the MD-Logic Artificial Pancreas System. (19) The study included 56 type I diabetic patients who were attending a diabetes camp, were 10-18 years old, and had used an insulin pump for at least 3 months. The study was done over 2 consecutive nights, during which each patient received an artificial pancreas one night and a continuous glucose monitor the other night, in random order. The primary endpoints were the number of hypoglycemic episodes (defined as glucose <63 mg/dL for at least 10 minutes), the total time that glucose levels were <60 mg/dL, and the mean overnight glucose levels.

There were fewer episodes of hypoglycemia recorded in the artificial pancreas group compared to the CGM group (7 versus 22, p=0.003). The median time that patients had a glucose level <60 was 0 minutes in both groups, but the time was significantly less in the artificial pancreas group (p=0.02). There was no significant difference in the mean glucose level in the artificial pancreas group compared to the CGM group (126.4 mg/dL versus 140.4 mg/dL).

Ongoing Clinical Trials

Outpatient Study to Evaluate Safety and Effectiveness of the Low Glucose Suspend Feature (ASPIRE) (NCT01497938) (20): This study is the in-home arm of the ASPIRE study evaluating the Paradigm Low Glucose Suspend (LGS) System; the in-clinic arm is described above. (18) The study is including 260 patients age 16 to 70 with type 1 diabetes. Patients will be randomized to a treatment arm that uses the Paradigm® VEO™ Pump and the LGS feature on or a control arm that uses a Paradigm® VEO™ Pump without the LGS feature. Patients will use the devices continuously for 5 months. The main objective of the study is to evaluate whether home use of the LGS feature is safe i.e., not associated with glycemic deterioration. The primary study outcome is a comparison between groups in change in HbA1C from baseline to the end of the 5-month period. The estimated date of study completion is June 2013.

Comparing Self-Monitored Blood Glucose (SMBG) to Continuous Glucose Monitoring (CGM) in Type 2 Diabetes (REACT3) (NCT01237301) (21): This study is including adult patients with type 2 diabetes who have an HbA1c of at least 7%. Patients are being randomized to unblinded use of a CGM device or to self-monitoring of blood glucose with fingersticks 4 to 7 times a day. The expected date of study completion is November 2013. The study is ongoing but is no longer recruiting participants; total sample size is estimated at 136.

Use of Continuous Glucose Sensors by Adolescents With Inadequate Diabetic Control (CGM-Teens) (NCT00945659) (22): This RCT is comparing continuous glucose monitoring, CGM plus behavioral therapy, and standard care in adolescents between the ages of 11 and 16 who have had type 1 diabetes for at least 2 years and who are not achieving targeted HbA1c levels (>7.5%). The primary outcome is change in HbA1c levels. The expected date of study completion is November 2013. The study is currently recruiting participants; estimated total enrollment is 150 patients.

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers

In response to requests, input was received from 1 physician specialty society and 4 academic medical centers while this policy was under review in 2008. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. Those providing input concurred that this technique, particularly intermittent glucose monitoring, was helpful in a subset of patients with diabetes. Reviewers commented that this monitoring can improve diabetes care by reducing glucose levels (and improving HbA1c) and/or by reducing episodes of hypoglycemia. Reviewers believed that there was persuasive information from case reports to demonstrate the positive impact of intermittent glucose monitoring.

Summary

The available studies demonstrate that glucose monitoring may improve glucose control in type I diabetic patients. However, the data on the impact of long-term continuous glucose monitoring are still limited. Studies such as that of the Juvenile Diabetes Research Foundation suggest that more frequent use of continuous glucose monitors may result in better outcomes, but this finding is not consistent across all available studies. In addition, the magnitude of effect is modest, suggesting that either the efficacy is of a small magnitude or that only a subset of patients benefit from this type of monitoring. Thus, the impact of CGM use on glucose control for the general diabetic population is uncertain, and CGM is considered investigational for the purpose of improving glucose control in the general diabetic population.

CGM provides more data points on glucose levels, and also provides information about trends. This additional information is most likely to benefit subgroups of diabetic patients, i.e. those patients with type I diabetes who do not have adequate control, including episodes of hypoglycemia, despite use of current best practices including multiple (4 or more) daily checks of blood glucose and use of an insulin pump. Based on the available data and supported by strong clinical input, intermittent, i.e., 72-hour, glucose monitoring may be considered medically necessary in those whose type 1 diabetes is poorly controlled, despite use of best practices.

Using a rationale similar to that noted above for intermittent monitoring, continuous monitoring can also be used in diabetic subpopulations. Continuous glucose monitoring may be considered medically necessary to provide additional data for management of those who have recurrent, unexplained, severe hypoglycemia that puts the patient or others at risk, despite use of current best practices, and also for pregnant patients with type I diabetes.

There are insufficient data on the impact of CGM systems on health outcomes in patients with type 2 diabetes. Few studies have focused on this population, and it is not clear what subset of patients with type 2 diabetes might benefit from intermittent or continuous glucose monitoring.

There are two small RCTs that report that use of an artificial pancreas device reduces hypoglycemic episodes. However, these trials are small and performed over very short time periods in controlled environments. In addition, no artificial pancreas device has received FDA-approval. Due to the limited evidence and lack of approved devices, use of artificial pancreas systems is considered investigational.

Practice Guidelines and Position Statements

In 2011, the American Diabetes Association made the following recommendations concerning continuous glucose monitoring (23):

  • CGM in conjunction with intensive insulin regimens can be a useful tool to lower A1c in selected adults (age at least 25 years) with type 1 diabetes. (Level of evidence A)
  • Although the evidence of A1c lowering is less strong in children, teens, and younger adults, CGM may be helpful in those groups. Success correlates with adherence to ongoing use of the device. (Level of evidence C)
  • CGM may be a supplemental tool to SMBG [self-monitoring of blood glucose] in those with hypoglycemic unawareness and/or frequent hypoglycemic episodes. (Level of evidence E)

In 2011, the Endocrine Society published a clinical practice guideline developed by a task force that included the following recommendations on continuous glucose monitoring (24):

  1. Real-time continuous glucose monitoring (RT-CGM) in adult hospital settings
    1. We recommend against the use of RT-CGM alone for glucose management in the intensive care unit or operating room until further studies provide sufficient evidence for its accuracy and safety in those settings.
  2. Children and adolescent outpatients
    1. We recommend that RT-CGM with currently approved devices be used by children and adolescents with type 1 diabetes mellitus who have achieved HbA1c levels below 7.0%.
    2. We recommend RT-CGM devices be used with children and adolescents with type 1 diabetes who have HbA1c levels 7.0% or higher who are able to use these devices on a nearly daily basis.
    3. We make no recommendations for or against the use of RT-CGM by children with type 1 diabetes who are less than 8 yr of age.
    4. We suggest that treatment guidelines regarding use of RT-CGM be provided to patients.
    5. We suggest the intermittent use of CGM systems designed for short-term retrospective analysis in pediatric patients with diabetes in whom clinicians worry about nocturnal hypoglycemia, dawn phenomenon, and postprandial hyperglycemia; in patients with hypoglycemic unawareness; and in patients experimenting with important changes to their diabetes regimen.
  3. Adult outpatients
    1. We recommend that RT-CGM devices be used by adult patients with type 1 diabetes who have HbA1c levels of at least 7.0% and who have demonstrated that they can use these devices on a nearly daily basis.
    2. We recommend that RT-CGM devices be used by adult patients with type 1 diabetes who have HbA1c levels less than 7.0% and who have demonstrated that they can use these devices on a nearly daily basis.
    3. We suggest that intermittent use of CGM systems designed for short-term retrospective analysis may be of benefit in adult patients with diabetes to detect nocturnal hypoglycemia, the dawn phenomenon, and postprandial hyperglycemia, and to assist in the management of hypoglycemic unawareness and when significant changes are made to their diabetes regimen.

References:

  1. Blue Cross and Blue Shield Technology Evaluation Center (TEC). Use of Intermittent or Continuous Interstitial Fluid Glucose Monitoring in Patients with Diabetes Mellitus. TEC Assessments 2003; Volume 18, Tab 16.
  2. Wilson DM, Beck RW, Tamborlane WV et al. The accuracy of the FreeStyle Navigator continuous glucose monitoring system in children with type 1 diabetes. Diabetes Care 2007; 30(1):59-64.
  3. Gandhi GY, Kovalaske M, Kudva Y et al. Efficacy of continuous glucose monitoring in improved glycemic control and reducing hypoglycemia: a systematic review and meta-analysis of randomized trials. J Diabetes Sci Technol 2011; 5(4):952-65.
  4. Wojciechowski P, Rys P, Lipowska A et al. Efficacy and safety comparison of continuous glucose monitoring and self-monitoring of blood glucose in type 1 diabetes. Pol Arch Med Wewn 2011; 121(10):333-43.
  5. Langendam M, Luijf YM, Hooft L et al. Continuous glucose monitoring systems for type 1 diabetes mellitus. Cochrane Database Syst Rev 2012; 1:CD008101.
  6. Floyd B, Chandra P, Hall S et al. Comparative analysis of the efficacy of continuous glucose monitoring and self-monitoring of blood glucose in type 1 diabetes mellitus. J Diabetes Sci Technol 2012; 6(5):1094-102.
  7. 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):1469-76.
  8. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Effectiveness of continuous glucose monitoring in a clinical care environment. Diabetes Care 2010; 33(1):17-22.
  9. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. The effect of continuous glucose monitoring in well-controlled type 1 diabetes. Diabetes Care 2009; 32(8):1378-83.
  10. Newman SP, Cooke D, Casbard A et al. A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE). Health Technol Assess 2009; 13(28):iii-iv, 1-194.
  11. Mauras N, Beck R, Xing D et al. A randomized clinical trial to assess the efficacy and safety of real-time continuous glucose monitoring in the management of type 1 diabetes in young children aged 4 to <10 years. Diabetes Care 2012; 35(2):204-10.
  12. Ehrhardt NM, Chellappa M, Walker MS et al. The effect of real-time continuous glucose monitoring on glycemic control in patients with type 2 diabetes mellitus. J Diabetes Sci Technol 2011; 5(3):668-75.
  13. Vigersky RA, Fonda SJ, Chellappa M et al. Short- and long-term effects of real-time continuous glucose monitoring in patients with type 2 diabetes. Diabetes Care 2012; 35(1):32-8.
  14. Secher AL, Ringholm L, Andersen HU et al. The Effect of Real-Time Continuous Glucose Monitoring in Pregnant Women With Diabetes: A randomized controlled trial. Diabetes Care 2013 [Epub ahead of print].
  15. Voormolen DN, Devries JH, Franx A et al. Effectiveness of continuous glucose monitoring during diabetic pregnancy (GlucoMOMS trial); a randomised controlled trial. BMC Pregnancy Childbirth 2012; 12(1):164.
  16. Raccah D, Sulmont V, Reznik Y et al. Incremental value of continuous glucose monitoring when starting pump therapy in patients with poorly controlled type 1 diabetes: the RealTrend study. Diabetes Care 2009; 32(12):2245-50.
  17. Battelino T, Conget I, Olsen B et al. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia 2012; 55(12):3155-62.
  18. Garg S, Brazg RL, Bailey TS et al. Reduction in duration of hypoglycemia by automatic suspension of insulin delivery: the in-clinic ASPIRE study. Diab Technol Ther 2012; 14(3):205-9.
  19. Phillip M, Battelino T, Atlas E et al. Nocturnal glucose control with an artificial pancreas at a diabetes camp. N Engl J Med 2013; 368(9):824-33.
  20. Sponsored by Medtronic Diabetes. Outpatient Study to Evaluate Safety and Effectiveness of the Low Glucose Suspend Feature (ASPIRE) (NCT01497938). Available online at: clinicaltrials.gov . Last accessed February, 2013.
  21. Sponsored by the Park Nicollet Institute. Comparing Self Monitored Blood Glucose (SMBG) to Continuous Glucose Monitoring (CGM) in Type 2 Diabetes (REACT3) (NCT01237301): . Available online at: www.clinicaltrials.gov. Last accessed February, 2013.
  22. Sponsored by the Nemours Children's Clinic. Use of Continuous Glucose Sensors by Adolescents With Inadequate Diabetic Control (CGM-Teens) (NCT00945659) Available online at: www.clinicaltrials.gov. Last accessed February, 2013.
  23. American DA. Executive summary: standards of medical care in diabetes—2011. Diabetes Care 2011; 34(Suppl 1):S4-S10.
  24. Klonoff DC, Buckingham B, Christiansen JS et al. Continuous glucose monitoring: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96(10):2968-79.

Codes

Number

Description

CPT  95250  Ambulatory glucose monitoring of interstitial tissue fluid via a subcutaneous sensor for up to 72 hours;sensor placement, hook-up, calibration of monitor, patient training, removal of sensor, and printout of recording 
  95251 ; physician interpretation and report
ICD-9 Procedure     
ICD-9 Diagnosis  250.00 – 250.93  Diabetes mellitus range of codes 
HCPCS  A9276 Sensor; invasive (e.g., subcutaneous), disposable, for use with interstitial continuous glucose monitoring system, one unit=1 day supply (new code 1/1/08)
  A9277 Transmitter; external, for use with interstitial continuous glucose monitoring system (new code 1/1/08)
  A9278 Receiver (monitor); external, for use with interstitial continuous glucose monitoring system (new code 1/1/08)
  S1030  Continuous non-invasive glucose monitoring device, purchase (for physician interpretation of data, use CPT code) 
  S1031  Continuous non-invasive glucose monitoring device, rental, including sensor, sensor replacement, and download to monitor (for physician interpretation of data, use CPT code) 
ICD-10-CM (effective 10/1/14) E10.10-E13.9 Diabetes mellitus code range
ICD-10-PCS (effecitve 10/1/14)   ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this monitoring.
Type of Service  Medicine 
Place of Service  Outpatient 

 


Index

Continuous Glucose Monitoring
Glucose Monitoring, Continuous
GlucoWatch, Glucose Monitoring
MiniMed, Glucose Monitoring

 


Policy History

 

Date Action Reason
08/18/00 Add to Durable Medicine section New policy
12/15/00 Replace policy Benefits application section revised to include information regarding BlueCard or National Account
05/15/02 Replace policy Policy reviewed; policy state unchanged; reference to 2002 TEC Assessment included
12/18/02 Replace policy Policy updated to include FDA approval for Glucowatch in children; policy statement unchanged
12/17/03 Replace policy Policy updated focusing on randomized trials of Glucowatch and CGMS devices; policy statement unchanged
07/15/04 Replace policy Updated specifications for the GlucoWatch G2 Biographer added
11/09/04 Replace policy Literature review update for the period of October 2003 through August 2004; information on the Guardian CGMS added. Policy statement unchanged
09/27/05 Replace policy Literature review update for the period of August 2004 through June 2005; reference number 12 added. Policy statement unchanged
02/15/07 Replace policy Policy updated with literature review from June 2005 through December 2006. Information about real-time continuous monitoring added to description section. Policy statement changed to indicated that real-time continuous monitoring is also investigational. Reference numbers 1, 2, 15–19 added
04/09/08 Replace Policy  Policy updated with literature review. Reference numbers 20-25 added 
08/14/08 Replace policy  Policy updated with literature review; reference numbers 26, 28, and 29 added. Clinical input reviewed.
12/01/08 Replace policy Policy updated with literature review; reference numbers 26, 28, and 29 added. Clinical input reviewed. New policy statement added that intermittent (72 hours) glucose monitoring may be considered medically necessary when specific criteria are met; continuous (long-term) monitoring also may be considered medically necessary when specific, but different, criteria are met.
03/11/10 Replace policy Policy updated with literature review, reference numbers 31-34 added; policy statements unchanged
3/10/11 Replace policy Policy updated with literature review. Rationale extensively rewritten. References 14,16,19,20,23 and 24 added; other references renumbered or removed. Policy statements unchanged.
03/08/12 Replace policy Policy updated with literature review. References 3, 4, 9-11, 15-17 and 19 added; other references renumbered or removed. Policy statements unchanged.
03/14/13 Replace policy Policy updated with literature review through February 6, 2013. Policy statement added that artificial pancreases are considered investigational. The word “symptomatic” removed from third policy statement. References 5, 6, 14, 15, 17-20 added; other references renumbered or removed.