Continuous and Intermittent Monitoring of Glucose in the Interstitial Fluid* Printer-Friendly Version   

Medical Policy: 01.01.03 
Original Effective Date: May 2000 
Reviewed: November 2007 
Revised: February 2008 

This policy applies to all products unless specific contract limitations, exclusions or exceptions apply. Please refer to the member's coverage manual for benefit availability. Managed care guidelines related to referral authorization, and precertification of inpatient hospitalization, home health, home infusion and hospice services apply.

Description: 

Recently, measurements of glucose obtained from the interstitial fluid have been utilized as a technique for automatically measuring glucose values throughout the day. Although the time interval at which interstitial glucose is measured ranges from every 5 to 20 minutes, all such monitoring devices are commonly referred to as continuous glucose monitors.

These devices do not eliminate the need for fingerstick blood glucose measurements. They must be calibrated at least daily with fingerstick blood glucose readings and the interstitial fluid glucose readings must be validated by fingerstick blood glucose readings before any adjustments in insulin are made, even if the device is associated with an implanted insulin pump.

Examples of these devices include;   

• The continuous glucose monitoring system, marketed under the trade name CGMS® System Gold^TM , manufactured by Medtronic MiniMed, is a healthcare provider prescribed device. It uses a temporary sensor implanted in the subcutaneous tissues connected to an external pager-like device worn by the patient. The CGMS® System Gold^TM  is intended for occasional use when prescribed and evaluated by a physician or other qualified healthcare provider. It is to be used only as a supplement to, not a replacement for, standard invasive measurement. It provides average glucose readings every five minutes for up to three days. The CGMS® System Gold^TM is not intended to change patient management based on the numbers generated, but to guide future management of the patient based on response to documented trends. That is, these trends or patterns are only used to suggest when to take the fingerstick glucose measurements to better manage patients.
• The Guardian® RT Continuous Glucose Monitoring System from Medtronic MiniMed is a provider prescribed device that is owned by the patient, and designed for use over extended periods of time to provide real-time glucose readings and alarms twenty four hours a day.
• The Paradigm® Real-Time System, also marketed by Medtronic MiniMed, is a combination implantable glucose monitor and insulin pump. The device allows the diabetic patient to be alerted to fluctuating glucose levels and then the patient must confirm the reading with a finger stick glucose measurement before activating the insulin pump to administer additional insulin.  Note: This policy does not pertain to the Paradigm model 522 or 722 insulin pumps which may be used independently of the glucose monitoring component of the Paradigm Real-Time System. 
• The GlucoWatch G2® Biographer marketed by Cygnus® is a noninvasive device worn like a wristwatch, which measures glucose in the interstitial fluid through the skin with a constant low level electric current by the process of reverse iontophoresis.
• The DexCom STS CGMS system is also for use by those with diabetes mellitus who are age 18 and older. Information from the premarket approval data submitted to the FDA indicates that the system is indicated for use as an adjunctive device to complement, not replace, information obtained from standard home glucose monitoring devices which use fingerstick blood samples.  Other real-time CGM systems are being studied, including systems for the pediatric age group.  

Policy: 

Monitoring of glucose levels in the interstitial fluid via a subcutaneously implanted sensor (e.g., Mini-Med CGMS, Guardian® RT System and DexCom STS™ Continuous Glucose Monitoring System) as a technique of diabetic monitoring may be considered medically necessary for up to three days at a time for patients who are compliant with their care and continue to perform four fingerstick blood glucose levels each day of monitoring and when one of the following criteria is met:

• Unexplained frequent hypoglycemia episodes in a diabetic taking insulin
• Hypoglycemia unawareness in a diabetic taking insulin
• Suspected non-diabetic hypoglycemia, such as may occur with Nesidioblastosis (islet cell dysmaturation syndrome) and insulinoma.
• Discordant HbA1c and fingerstick blood glucose levels (such as the patient with consistent normal blood glucose levels at home but high HbA1c levels)
• Frequent nocturnal hypoglycemia
• Early morning fasting hyperglycemia in type 1 diabetics (generally due to inadequate overnight delivery of insulin and sleep-associated growth hormone release; known as the "dawn phenomenon")
• Prior to insulin pump therapy to determine basal levels, and follow-up to verify adequate levels
• Diabetic and pregnant or about to conceive
• Episodes of ketoacidosis or hospitalizations for glucose out of control

Continuous monitoring of glucose in the interstitial fluid beyond three days is considered investigational. Devices, with or without communication to an insulin pump, intended to monitor interstitial glucose beyond three days include, but are not limited to the GlucoWatch Biographer, the Guardian, and the DexCom.

Prior approval is recommended. Submit a prior approval now.

Rationale:

Data presented to the U.S. Food and Drug Administration (FDA) advisory committee meeting consisted of studies validating the correlation between the measurements of glucose in interstitial fluid with the blood glucose measurements made with home monitoring devices. While the individual values between the two may vary, in general, the panel found that the overall trends in glucose levels detected by frequent measurements produced potentially clinically important information. However, there were no clinical data presented regarding improvements in HbA1c measurements or a decreasing incidence of hypoglycemic episodes in those whose antidiabetic medications were managed based on more frequent readings of interstitial fluid glucose. However, members of the advisory panel felt that more frequent measurements should extrapolate to improved diabetic management. For example, prior studies have shown that HbA1c levels are lowest among patients who have the highest frequency of daily blood glucose measurements.

The key clinical outcomes regarding the clinical utility of interstitial measurements of glucose, using either the Continuous Glucose Monitoring Systems or the GlucoWatch G2 Biographer, relates to their ability to provide either additional information on glucose levels leading to improved glucose control, or to improve the morbidity and 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 are important to isolate the contribution of interstitial glucose measurements to the overall diabetic management.

This policy is based on a 2003 TEC Assessment which reviewed the published controlled trials and offered the following discussion.

GlucoWatch Biographer

Chase and colleagues reported the results of a trial of 40 children with poorly controlled Type 1 diabetes (HbA1c >8) who were randomized to diabetic management with or without glucose monitoring with a GlucoWatch device. Conventional glucose monitoring was performed 4 times daily in both groups. Those randomized to the treatment group were asked to wear the device 4 times per week for three months. After three months, all patients received Biographers and were followed up for six months. HbA1c values were determined at baseline and after one, three, six, and nine months. The median HbA1c level dropped from 8.9% to 8.4% in the treatment group, while in the control group the HbA1c increased from 8.6% to 9%. While this difference was statistically significant, it should be noted that the worsening of HbA1c in the control group was nearly as large in magnitude as the improvement in HbA1c seen in the Biographer group. There was no significant improvement in “fear of hypoglycemia” or quality of life between the two groups. In a second observational phase of the trial, all subjects were provided Biographer devices and observed over an additional six months. During this phase, the Biographer group maintained median HbA1c at 8.5%, and the control group improved median HbA1c to 8.6%, which was their original level. It was noted that the frequency of use of the Biographer declined over the course of the first phase of the study, and this may be why the Biographer group did not show further improvement in HbA1c over the subsequent 6 months of use.

Baseline characteristics of the two randomized study groups were reported to be without statistically significant differences. However, the baseline median HbA1c levels for these two groups were different by 0.3%, which is almost as large as the 0.4%–0.5% change observed within groups after provision of the Biographer, and this difference may have clinical significance. Also at baseline, slightly more patients in the control group used insulin pumps or received three or more insulin injections per day compared with the Biographer group, which had slightly more subjects receiving only two insulin injections per day. It is unknown whether these slight imbalances were a result of the small sample or whether there were any problems with randomization.

The authors do not discuss whether such differences might have influenced the observed results, but additional analyses adjusting for differences in potentially confounding baseline characteristics and exploring whether outliers could have influenced the results would be of interest. In addition, it is unclear whether subjects in the Biographer group received more frequent or more intense contact with physicians and the diabetes clinic. Biographer subjects were required to visit the clinic each week to download Biographer data; whereas the control group was able to fax back conventional fingerstick glucose meter data. This process may have provided more in-person opportunity for medical input in the Biographer group.

Interpretation of this study’s results should also take into consideration the observation that HbA1c levels may fluctuate over time, even without intervention, and variations of up to 1% may be observed clinically in the pediatric population. In this study, the control group’s HbA1c got worse during the intervention study, which partially contributed to the statistically significant difference between groups. Improvement in HbA1c has been observed in control groups in multiple other studies, most likely as a result of study effects (Hawthorne effect) in which participants in a trial achieve better compliance when results are being monitored. It is unclear why the control group got worse in this study, and this raises concerns over the reproducibility of the study.

Interpretation of the clinical significance of reducing HbA1c by 0.5% has been explored and both magnitude and durability of the improvement are important factors to consider. Eastman and colleagues presented an abstract of a decision analysis model based on the above study and reported that “the model predicts that treating 100 subjects under Biographer-guided standard care, if maintained for the life of the cohort, would prevent 20 cases of proliferative retinopathy, four cases of macular edema, six cases of blindness, 12 cases of clinical albuminuria, eight cases of end-stage renal disease, six cases of neuropathy and one amputation.” However, this model makes a variety of assumptions regarding the durability of the improvement.

In summary, Chase and colleagues conducted a small, randomized controlled trial and reported a small but statistically significant difference in the median HbA1c levels between groups after three months. However, the relatively small magnitude of incremental improvement in HbA1c levels needs to be interpreted in the context of potentially different baseline statistics between subjects in the two groups, potential study effects (Hawthorne effect) in the Biographer group in this unblinded trial, and potential influences of receiving more intense medical attention in the Biographer group. It would be very helpful to see the results of this trial confirmed by another larger, multicenter randomized controlled trial and to have further studies explore the durability of HbA1c improvements over time.

Continuous Glucose Monitoring Systems (CGMS)

Results of four randomized trials have been reported. The largest of them, which enrolled 128 adult patients with Type 1 diabetes, is available in abstract only.  Among the 109 patients completing the three-month trial (the dropout rate was 15%), there was no statistically significant difference in HbA1c levels. Mean HbA1c levels in both the control and study groups declined from 9% at baseline to 8.3% at three months. Similarly, in another randomized study of 75 patients, there was no statistical difference in HbA1c levels after the three-month intervention. The other randomized studies  included only 11 and 27 patients, respectively. In 2004, Tanenberg and colleagues reported on a study of 128 patients randomized to insulin therapy adjustments using data from either the CGMS or self-monitoring of blood glucose (SMBG) using a home blood glucose monitor over a 12-week period. At 12 weeks, HbA1c levels and hyperglycemic event frequency and duration did not differ with any statistical significance in the treatment groups. However, at 12 weeks, events of hypoglycemia (glucose < or = 60 mg/dL) were found to be significantly shorter in the CGMS group than in the SMBG group (49.4 +/- 40.8 vs. 81.0 +/- 61.1 minutes per event, p = .009). The authors concluded that durations of hypoglycemia can be further reduced by adjusting insulin therapy with data from the CGMS rather than using SMBG data alone. Nevertheless, the biochemically defined measurements of hypoglycemia (without accompanying evidence of symptoms or a clinically significant hypoglycemic event) are not compelling outcomes. The clinical significance of these test results has not been established, i.e., there is insufficient evidence showing the link between increased duration of asymptomatic hypoglycemia and subsequent clinical outcomes.

2006 — 2007 Update

Additional studies continue to evaluate continuous glucose monitoring systems. Lagarde and colleagues found a slight improvement in HbA1c levels using CGMS compared to controls in children with Type 1 diabetes. However, the difference did not reach statistical significance (p = 0.13). In a European study using a cross-over design, Deiss and colleagues reported that CGMS did not decisively influence glycemic control of the total study cohort of children and adolescents with Type 1 diabetes.  They suggested that more frequent use of CGMS at shorter intervals may be of greater value. A recent review in The Medical Letter on Drugs and Therapeutics raised questions about the accuracy of these systems.

Garg, et al. reported in 2006 that in 91 patients with diabetes (75 were Type 1) real-time continuous glucose monitoring was able to reduce glycemic excursions by reducing hyperglycemia without increasing the risk of hypoglycemia. They also indicated that this type of monitoring may reduce long-term complications of diabetes. Recently, Deiss, et al. reported on a three-month study of 81 children and 81 adults with stable Type 1 diabetes who had HbA1c levels of 8.1% or greater. Patients were randomized to continuous real-time monitoring, continuous monitoring for three days every two weeks, or self-monitoring of blood glucose. At three months, 50% of patients with continuous real-time monitoring had a decrease in HbA1c of at least 1% compared to 37% of those with intermittent continuous monitoring, and 15 % of controls. These results suggest that continuous glucose monitoring may have potential for improving control in patients with diabetes; however, as the authors note, additional work is needed to determine long-term efficacy, clinical feasibility in patients with varying levels of glycemic control, and effect on rates of hypoglycemia.

Top

Procedure Codes and Billing Guidelines: 

• To report provider services, use appropriate CPT** codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9 diagnostic codes. 
• CPT code 95250 for the CGMS®; Glucose monitoring for up to 72 hours by continuous recording and storage of glucose values from interstitial tissue fluid via a subcutaneous sensor (includes hook-up, calibration, patient initiation and training, recording, disconnection, downloading with printout of data).
• CPT code 95251 Ambulatory continuous glucose monitoring of interstitial tissue fluid via a subcutaneous sensor for up to 72 hours; physician interpretation and report  
• HCPCS code S1030 to report purchase of a continuous noninvasive glucose monitoring device, such as the GlucoWatch.
• HCPCS code S1031 to report rental of continuous noninvasive glucose monitoring device, such as the GlucoWatch.
• HCPCS code A9276 Sensor; invasive (e.g., subcutaneous), disposable, for use with interstitial continuous glucose monitoring system, 1 unit = 1 day supply
• HCPCS code A9277 Transmitter; external, for use with interstitial continuous glucose monitoring system
• HCPCS code A9278 Receiver (monitor); external, for use with interstitial continuous glucose monitoring system    

Top

Selected References: 

• The Medical Policy Reference Manual developed by the Blue Cross Blue Shield Association Health Management Systems, based on Technology Evaluation Center (TEC) criteria.
• A review of the medical literature and recommendations from the Medical Policy Advisory Council (MPAC), which assists Wellmark’s medical directors in the development of medical policies. MPAC is comprised of practicing physicians from Iowa and South Dakota.
• Technology assessment brief. Continuous Glucose Monitoring System. Hays Alert 2000, June; vol. 3 (6): 5-6. 
• Tamada JA, Garg S, Jovanovic L, Pitzer KR, Fermi S, Potts RO, the Cygnus research teams. Noninvasive Glucose Monitoring, comprehensive clinical results. JAMA, 1999; 282:1839-1844. 
• Bode BW, Gross TM, Thornton KR, Mastrototaro JJ. Continuous glucose monitoring used to adjust diabetes therapy improves glycosylated hemoglobin: a pilot study. Diabetes Research and Clinical Practice 46 (1999) 183-190.
• 2003 TEC Assessment: Continuous or Intermittent Monitoring of Interstitial Glucose. Technology Evaluation Center; Available on line at http://www.bcbs.com/betterknowledge/tec/ 
• Chase H, Roberts P, Wightaman MD, et al. Use of the GlucoWatch biographer in children with type 1 diabetes. Pediatrics 2003;11(4): 1-10.
• Guerci B, Floriot M, Bohme P, et al. Clinical performance of CGMS in type 1 diabetic patients treated by continuous subcutaneous insulin infusion using insulin analogs. Diabetes Care2003;26:582-589.
• Tice JA. Continuous glucose monitoring devices in diabetes mellitus. California Technology Assessment Forum; 2003, October 8. 47 p.
• ECRI. Continuous subcutaneous glucose monitoring system for diabetes patients. Plymouth Meeting (PA): ECRI Health technology Information Service; 2002 August Target Report 519; 11 p. (ECRI Target Database). 
• ECRI. Continuous Subcutaneous Glucose Monitoring Systems for Diabetes. Plymouth Meeting (PA): ECRI Health technology Information Service; 2005 Jun 02. 10p. (ECRI Hotline Response).
• Chico A, Vidal-Rios P, Subira M et al. The continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with type 1 and type 2 diabetes but is not better then frequent capillary glucose measurements for improving metabolic control. Diabetes Care 2003; 26(4):1153-7.
• Chase HP, Kim LM, Owen SL et al. Continuous subcutaneous glucose monitoring in children with type 1 diabetes. Pediatrics 2001; 107(2):222-6.
• Tanenberg R, Bode B, Lane W et al. Use of the Continuous Glucose Monitoring System to guide therapy in patients with insulin-treated diabetes: a randomized controlled trial. Mayo Clin Proc 2004; 79(12):1521-6.
• ECRI. Combined insulin pump and continuous glucose monitoring system for diabetes management. Plymouth Meeting (PA): ECRI Health technology Information Service; 2006 May 22. 9 p. (ECRI Hotline Response).
• ECRI. Guidelines for self-monitoring of glucose in patients with diabetes.  Plymouth Meeting (PA): ECRI Health technology Information Service; 2006 January 04. 9 p. (ECRI Hotline Response).
• Garg S, Zisser H, et al.  Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: a randomized controlled trial.  Diabetes Care. 2006 Jan;29(1):44-50.
• Deiss D, Bolinder J, Riveline JP, et al. Improved glycemic control in poorly controlled patients with type-1 diabetes using real-time continuous glucose monitoring. Diabetes Care 2006: 29(12):2730-2.
• Continuous glucose monitoring. Med Lett Drugs Ther 2007; 49(1254):13-5. 

Top

Wellmark Blue Cross and Blue Shield
Medical Policy Analyst
Station 304
636 Grand Ave
Des Moines, Iowa 50309

*Prior Approval is recommended for this policy.

**Current Procedural Terminology © 2008 American Medical Association. All Rights Reserved.

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.