The first major multi-center human clinical trial to determine the benefits of using continuous glucose monitors in managing type 1 diabetes and improving the clinical outcome of patients

Publications to date:

The New England Journal of Medicine (October 2008) - Results of trial at 6 months

Diabetes Care (May 2009) - Results for Participants with HbA1c levels under 7

Diabetes Care (August 2009) - Results of trial at 12 months

Diabetes Care (August 2009) - CGM Results by Frequency of Use


Overview

Over the past 12 months, JDRF has added immeasurably to the information available about the clinical effectiveness of continuous glucose monitors - devices that track blood sugar levels on a real-time basis and provide information to help better manage diabetes - through its groundbreaking CGM human clinical trials.

Peer-reviewed papers detailing some of the exciting results of these multi-site studies have been published in several top medical research journals, including the New England Journal of Medicine, and - just this week - Diabetes Care.  Those papers document the beneficial impact CGM devices can have in diabetes care.


Major Findings

Based on the published results of the JRDF CGM Trials, it is now clear that:

• CGM devices help people with diabetes manage their disease significantly better than traditional blood sugar monitoring methods;

• People of all ages - adults, teenagers, and children - who use CGM devices regularly (at least 6 days per week) can see positive results in managing their diabetes;

• Improvements are not just seen in the months after adding CGM to diabetes management,  but can continue out a full year - the longest time period for which the trial results have been studied so far;

• CGM devices improve diabetes management without increasing the incidence of dangerous low blood sugars, or hypoglycemia, a major hurdle in tightly controlling type 1 diabetes; and

• Even people who already have their diabetes in control - meeting the recommended standards for long-term blood sugar tests - see improvements by using CGM devices. 

Why is the Impact of CGM Devices So Important?

Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of diabetes, such as blindness and kidney disease.  But the fear of low blood sugar emergencies often prevents people from achieving tight control - and remains a constant concern for those who manage their diabetes well.  The landmark Diabetes Control and Complications Trial (DCCT) showed that with intensive insulin therapy, excellent blood glucose control was obtained, but at the expense of a considerable increase in hypoglycemia.  The JDRF CGM Trials have shown that, by using CGM devices, people with type 1 diabetes can maintain excellent blood sugar control, while also reducing hypoglycemia.

What Improvements Have Occurred as a Result of the Trials?

As a direct result of the JDRF CGM Trials, more insurance carriers reimburse for CGM devices than ever before, providing more people with diabetes the opportunity to better control their disease.  Since the publication of the initial trial findings, most major medical insurers have increased or begun coverage of CGM, in full or in part.  They include: Aetna, Blue Cross Blue Shield of MA, Blue Cross Blue Shield of IL, CIGNA, Harvard Pilgrim (MA), Highmark Blue Cross Blue Shield (PA), Humana, Kaiser Permanente Northern and Southern CA, Tufts (MA), United, Wellpoint/Anthem.

Also as a result of the JDRF trial, CGM is now included in national standards of care for type 1 diabetes, making doctors more likely to prescribe them for patients.

In addition, since the trials began, the course for the development of a closed-loop artificial pancreas - a device that uses a sophisticated algorithm to combines a CGM device with an insulin pump to mimic how a pancreas works - has been fast-tracked.   The clear benefits of CGM make the development of an artificial pancreas the next logical step in research leading to cures and better treatments for people with type 1 diabetes.

The Trials

JDRF's CGM study was a randomized, controlled trial involving 451 people with type 1 diabetes, ranging in age from 8 to 72 years-old.  The trial was conducted at 10 sites, which included academic, community, and managed care based practices, coordinated by the Jaeb Center for Health Research in Tampa, Florida.

The clinical trial sites were: the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children's Clinic - Jacksonville, FL, the Lucile Packard Children's Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University.

Participants were assigned either to a group using CGM devices, or to a control group using standard blood sugar monitoring.  They were followed for 26 weeks, and then another 26 weeks, to assess effects on blood sugar control, principally assessed by measurement of the HbA1c level.  At enrollment into the study, one cohort of patients had HbA1c levels between 7 and 10%; another already had HbA1c levels below 7%.  (The goal for adults with type 1 diabetes generally is a level below 7%, and for children and adolescents below 7.5-8%.)  Three age groups were analyzed separately: 8 to 14 years of age, 15 to 24 years of age, and 25 years of age or older.

NEJM - Showing Improvements in First Six Months of CGM Use

The six month results of the trial reported in the New England Journal of Medicine in October of 2008, showed that patients with type 1 diabetes who used CGM devices to help manage their disease experienced significant improvements in blood sugar control; improvements were greatest for CGM patients 25 years of age or older, whose HbA1c levels decreased (improved) during the study by an average of 0.53% compared with control patients.  Improvements in secondary measurements were also significantly greater in CGM patients, including the percentage of patients able to achieve an HbA1c level below 7%, a 10% relative drop in HbA1c level, or a 0.5% absolute drop in HbA1c.  The improvements in HbA1c occurred without an increase in hypoglycemia, which is the worry when attempting to tighten glucose control.

In children aged 8-14 years old, the average decrease in HbA1c was not significantly different in the CGM and control groups; however, those in the CGM group were more likely to lower their HbA1c by at least 10% and achieve HbA1c levels below 7% compared with the control group.  Fifteen-to-24-year-old CGM patients, as a group did not experience significant improvements in glucose control compared with the control group. Adults 25 and older tended the use the devices most regularly - more than six days per week.

Additional analysis, described below and published in Diabetes Care, provided more insight into factors influencing the use of CGM.


Diabetes Care - CGM Benefits Tied to Regular Usage

According to this paper, regular use of CGM devices is the principal factor in achieving better diabetes control, rather than the age of people using the monitors, or other demographic, clinical, or psychosocial factors.

Initial findings from the trials published in the New England Journal of Medicine had noted that improvements in diabetes control  were most significant among those in the 25 and older age group; children, teenagers and young adults saw less dramatic improvements.  But this study, looking at those same trial results in a different way, show that after adjusting for the frequency of CGM use, the association of age group with improvements in HbA1c was no longer significant - in other words, participants in the trial in all age groups, from children through adults, who used CGM devices six days per week or more saw similar levels of improvement in their diabetes control. In addition, the study found that regular use of blood glucose testing prior to beginning CGM therapy was an excellent predictor of regular CGM use and thus of improvement in glucose control.


Diabetes Care - Results Persist Over 12 Months, While Hypoglycemia Goes Down

The study showed that people who continue using CGM for up to a year continue to see the good diabetes control that earlier trial results had shown participants achieved when first switching to the devices - actually lowering the incidence of hypoglycemia.

People who began the trial with HbA1c levels above 7% saw a reduction in HbA1c mainly in the first eight weeks of the study, and then remained relatively stable through the next 44 weeks.  Among participants who began the trials with an HbA1c below 7%, they remained within that target range over the entire 12 months of the study.   CGM devices helped patients achieve that control while also experiencing a remarkably low rate of severe hypoglycemic events during the second six months of the study.  Severe hypoglycemic events - which required the assistance of another person or medical professional - were experienced by 10% of the study participants during the first six months of the trial, but only by 4% in the second six months.  The rate of severe hypoglycemic events fell from 21.8 events per 100 person-years during the first six months to 7.1 events per 100 person-years during the second six months. The rate was not associated with the HbA1c level of the trial participants at the time the study began.  In fact, the rate of severe hypoglycemia in people using CGM devices was markedly lower than in the DCCT intensive treatment group - seven hypoglycemia events compared with 62 in the DCCT trial - even though the mean HbA1c of JDRF trial participants at 6.8% was lower than the DCCT trial participants' level of 7.1%.


Diabetes Care - Good Results for People Already in Good Control

Results of another cohort of the JDRF Trials showed that CGM use also benefits those who already have their diabetes under good control - not just those who are having difficulty managing blood sugar.  The paper demonstrated a number of significant benefits for people in good control using CGM devices:

• CGM use maintained HbA1c
• It helped people under 7% stay under 7%
• It lowered HbA1c without severe hypoglycemic events.

According to the study, people using CGM spent almost two hours more time per day in a target blood sugar range of 71 to 180 mg/dL compared with the control group, and about half an hour less time per day with glucose values in the potentially dangerous hypoglycemia range.  More important, the study showed that using CGM devices enables people who have achieved excellent control (with HbA1c levels below 7 percent) to maintain that control while cutting down on the frequency of low blood sugars, or hypoglycemia.