Drug Information Center

• Drug Information Group
• Department of Pharmacy Practice
• About Us
• People
• Potential Partnerships
• The RxPress
• Residency Program
• Frequently Asked Questions
• Contact Us
• Feedback

Is continuous glucose monitoring associated with improved glycemic control in patients with type 1 diabetes?

Background
Type 1 diabetes mellitus is a metabolic disorder caused by insulin deficiency resulting from the destruction of the insulin-producing pancreatic beta cells.¹ The onset of type 1 diabetes is usually seen at younger ages, but adult-onset may also occur. Over 1 million individuals in the United States have type 1 diabetes, which accounts for 5% to 10% of all cases of diabetes.^1,2 The goals of treatment are directed at reducing symptoms of hyperglycemia, and reducing the onset and progression of diabetes-related complications such as retinopathy, nephropathy, and neuropathy. Glycemic control is important in reducing the risk of complications in patients with diabetes. Hemoglobin A1c (HbA1c) measurements are the gold standard for assessing long-term glycemic control, and a target of less than 7% is currently considered appropriate for patients with diabetes. Treatment of type 1 diabetes is achieved with insulin therapy and self-monitoring of blood glucose to maintain appropriate glucose levels. However, despite the use of insulin therapy and glucose monitoring, diabetes-related complications may still occur due to the fact that glycemic goals are not always met.³ Tighter control of blood glucose has been suggested as a means to reduce the risk of complications.

Intensive insulin therapy
The effects of tight glycemic control and intensive insulin therapy have been explored in studies such as the Diabetes Control and Complications Trial (DCCT), and the Epidemiology of Diabetes Interventions and Complications Study (EDIC).^4,5

The DCCT showed that intensive treatment (eg, 3 or more daily insulin injections or an insulin pump) with the goal of maintaining blood glucose concentrations close to the normal range decreased the overall incidence and severity of microvascular complications.⁴ The EDIC study examined the impact of intensive insulin therapy on the incidence of microvascular and cardiovascular complications and concluded that intensive glucose control decreased the incidence of cardiovascular events by 42%.⁵ Both trials highlighted the importance of intensive insulin therapy and tight glycemic control in patients with type 1 diabetes, and in the process proved that the most significant side effect of intensive treatment was hypoglycemia, which can be a hindrance in the implementation of intensive insulin therapy.⁵

Continuous glucose monitoring
Despite the increased use of insulin pumps and multiple injection regimens, intensive treatment of type 1 diabetes mellitus often does not achieve recommended HbA1c levels.³ Although self-monitoring of blood glucose plays an important role in achieving target HbA1c levels, few patients with type 1 diabetes measure glucose levels after each meal or overnight; therefore, continuous glucose monitoring is an important tool in preventing diabetes complications and achieving target HbA1c levels. Continuous glucose monitoring has a role in all types of diabetes.

In a randomized, clinical trial assessing the effectiveness of continuous glucose monitoring in pregnant women with diabetes, it was determined that continuous-monitoring resulted in a reduction of HbA1c levels in the third trimester and in the risk of macrosomia (ie, very high birth weight), which is the most common complication of pregnancy in women with diabetes.⁶

There are several continuous-glucose monitoring devices that can be used by children and adults. The devices generally have 3 components: a sensor, a transmitter, and a receiver.⁷ The sensor is applied to the back of the arm or the abdomen and can be worn continuously for up to 7 days depending on the type of device. It is inserted subcutaneously with a 5 mm deep filament, which measures glucose in the interstitial fluid. The wireless transmitter, which is attached to the sensor, sends glucose readings to the receiver anywhere within a 10-foot range. The receiver contains a built-in blood glucose meter for calibration and confirmatory blood glucose tests, and displays past, present, and future glucose information. The system has early warning alarms that can be customized to alert the patient 10 to 30 minutes in advance of hypo- or hyperglycemia.⁷

Evaluation of continuous glucose monitoring
The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group was a randomized, multicenter clinical trial conducted to evaluate the safety and efficacy of continuous glucose monitoring in adults and children with type 1 diabetes.³ All eligible patients were 8 years of age or older with a diagnosis of type 1 diabetes at least 1 year before randomization. All patients either used an insulin pump or received at least 3 daily insulin injections, had an HbA1c of 7% to 10%, and had not used continuous glucose monitoring at home in the 6 months leading up to the trial.

Patients completed a run-in phase using a continuous glucose monitor and were required to wear a sensor for at least 6 of 7 days before randomization, with a minimum of 96 hours of glucose values; home blood glucose monitoring was performed at least 3 times daily.³ Patients in the continuous-monitoring group were given one of several continuous glucose monitoring systems (DexCom Seven, Freestyle Navigator, or MiniMed Paradigm Real-Time Insulin Pump and Continuous Glucose Monitoring System) and were instructed to use the device on a daily basis. Patients in the control group were given blood glucose meters and test strips and asked to perform home blood glucose monitoring at least 4 times daily. Scheduled visits were conducted at 1, 4, 8, 13, 19, and 26 weeks with one telephone contact between each visit. HbA1c was measured at baseline and at 13 and 26 weeks. The primary outcome was the change in mean HbA1c level from baseline to 26 weeks.

A sample size of 322 patients underwent randomization with 165 patients assigned to the continuous-monitoring group and 157 to the control group.³ Patients were stratified according to age group (> 25 years, 15-24 years, and 8-14 years) and HbA1c level (< 8.0% and > 8.0%). Overall, 219 patients had an HbA1c level of 7.0% to 8.0%, 83 patients had an HbA1c of 8.1% to 8.9%, and 20 patients had an HbA1c level of 9.0% or greater. Patients included in the trial tested their blood glucose an average of 6.5 + 2.5 times a day.

In the primary analysis, a significant between-group difference in the change in HbA1c level from baseline to 26 weeks was seen in patients who were 25 years of age or older favoring the continuous-monitoring group (mean difference -0.53%; p<0.001), but not in those 15 to 24 years of age (+0.08; p=0.52) nor in those 8 to 14 years of age (-0.13; p=0.29).³ At 26 weeks, among patients in the continuous-monitoring group who were 25 years of age or older, there were improvements in all measures of glycemic control as compared with the control group.

In the secondary analysis, more patients in the continuous-monitoring group had a relative reduction of 10% or more in the mean HbA1c level, as compared with baseline (p=0.003), and more achieved the target HbA1c of less than 7.0% (p=0.005), as recommended by the American Diabetes Association.³ Among patients who were 15 to 24 years of age, the mean decrease in HbA1c levels from baseline to 26 weeks was approximately 0.2% in both study groups. Among patients who were 8 to 14 years of age, the mean decrease in HbA1c levels was 0.37% in the continuous-monitoring group, which did not differ significantly from the decrease of 0.22% in the control group. However, secondary indexes of glycemic control were improved with a relative reduction of 10% or more in HbA1c level from baseline (p=0.04), and more patients had HbA1c levels of less than 7.0% (p=0.01). There were no significant differences in the incidence of severe hypoglycemic episodes between study groups according to age.

The authors observed that the benefit associated with continuous glucose monitoring was strongly related to age.³ A significant difference in the primary analysis of the change in HbA1c levels from baseline to 26 weeks was seen in the predefined group of patients who were 25 years of age or older but not in the 2 groups of patients who were younger. More patients in the continuous-monitoring group than in the control group had an HbA1c level of less than 7.0% without having a severe hypoglycemic event. In the other age groups, (8-14 years and 15-24 years) comparisons between study groups showed little to no benefit of continuous glucose monitoring.

The observation noted in subjects over 25 years of age and those 8 to 14 years of age who met the secondary indexes and had a relative reduction of 10% or more in HbA1c levels from baseline values was important since DCCT showed that a relative reduction of 10% is associated with a reduction of more than 40% in the rate of development and progression of early diabetic retinopathy.⁸

Conclusion
The randomized trial carried out by the Juvenile Diabetes Research Group gave insight to the impact of continuous glucose monitoring on HbA1c levels in patients with type 1 diabetes. For many patients, intensive insulin therapy has not proven sufficient to achieve the HbA1c levels targeted by the DCCT trial; as such, continuous glucose monitoring is one addition that can be made to assist patients in achieving those target levels.

The use of the glucose monitoring device for ongoing measurement also targeted the often seen problem of hypoglycemia, a hindrance to implementing intensive insulin therapy in patients. The study showed significantly better results for older adults in the continuous-monitoring group as these adults used the continuous glucose monitor more often than those in other groups (an average of 6 or more days per week). Those patients age 15 to 24 years had the lowest use rate with only 30% using the device 6 days or more per week and the youngest patients had a 6-day use rate of 50%. The increased results seen in the older adults lends credence to the fact that continuous glucose monitoring improves HbA1c levels and enhances the management of type 1 diabetes in adults who are more adherent and have the motivation to use this device. Overall, the subjects included in the trial were already committed to intensive insulin therapy with either insulin pumps or multiple daily injections and had better than average HbA1c levels, therefore, the trial is not readily applicable to less motivated patients or those who are not in such a well-controlled environment. Intensive insulin therapy and continuous monitoring are both beneficial in achieving the target HbA1c levels; however, strategies to improve adherence and glucose monitoring in younger patients are needed.

References

1. Triplitt CL, Reasner CA, et al. Diabetes Mellitus. In: DiPiro JT, Talbert RL, et al. Pharmacotherapy: A Pathophysiologic Approach. 6^th ed. New York, NY: McGraw-Hill; 2005:1333-1367.
2. CDC resource page. Centers for Disease Control and Prevention Web Site. http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Accessed November 24, 2008.
3. The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008;359(14):1464-1476.
4. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complication in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
5. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643-2653.
6. Murphy HR, Rayman G, et al. Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomized clinical trial. BMJ. 2008;337:a1680.
7. Freestyle Navigator Continuous Glucose Monitoring [package insert]. Abbott laboratories, Abbott Park, IL; January 2008. http://www.freestylenavigator.com/en_US/content/document/FSN-Brochure-ART09624_Rev-B.pdf. Accessed November 26, 2008.
8. Genuth S. Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes. Endocr Pract. 2006;12(suppl 1):34-41.

by Olamide Davies