Is the use of continuous glucose monitoring alone superior versus its use with blood glucose monitoring?
Traditionally, glucometers required pricking a fingertip with a lancing device to obtain blood glucose (BG) levels at that point in time. However, on December 20, 2016, FDA approved the Dexcom G5 Continuous Glucose Monitoring (CGM) System, an externally worn glucose sensor that determines BG values every 5 minutes in real-time for up to seven days. CGM delivers glucose patterns to help in long-term adjustments to treatment plans to keep BG in a safe range. Also, it provides the rate of BG changes and alerts when glucose values are approaching hyperglycemic or hypoglycemic levels. However, no clinical trials have confirmed the safety and effectiveness of CGM without Blood Glucose Monitoring (BGM).
A multicenter randomized noninferiority clinical trial was conducted at 14 endocrinology sites in the U.S. Participants were clinically diagnosed with T1D ≥1 year(s), HbA1c ≤9.0%, at least ≥18 years old, used insulin pump for at least 3 months, able to manage insulin administration and glucose monitoring, and comply with the study protocol. A run-in phase of 2-10 weeks initiated by 276 patients, led to the 6 months trial. Two parts of the run-in phase were using Dexcom CGM at study entry to record glucose concentrations not visible to the participant for 14 days (baseline data) and standard CGM for 2–8 weeks for CGM training. Participants were randomly assigned in a 2:1 ratio to the CGM-only or CGM + BGM study arms. Both arms performed BGM when CGM fasting or during the day was >300 mg/dL. If confirmed by BGM, then Abbott Precision Xtra was used to measure ketone levels. The CGM system measured BG from interstitial fluid in the range of 40-400 mg/dL every 5 min and the BGM used the CONTOUR Next device. Follow-ups occurred at 3, 6, 13, 19, and 26 weeks to assess compliance, additional training, and to determine required changes in diabetes management.
The purpose of this study was to determine whether the use of CGM without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in well-controlled adults with type 1 diabetes (T1D). The primary outcome was CGM-measured time in range of 70–180 mg/dL over the trial period of 26 weeks by using the ANCOVA model adjusted for baseline time in range and site as a random effect. The logistic regression model compared no worsening of HbA1c by >0.3% and no severe hypoglycemia, adjusted for baseline A1c and site as a random effect. Also, it compared the subject with at least one blood ketone level of ≥0.6 mmol/L and ≥1.0 mmol/L between treatment groups. The secondary outcomes included CGM measures of mean glucose, episodes of hypo/hyperglycemia, and changes in HbA1c. Safety outcomes highlighted the severe hypoglycemic or hyperglycemic events and DKA. A sample size of 225 subjects was determined for a noninferiority limit of 7.5% difference between the CGM-only or CGM + BGM groups.
The study strengths included a high degree of participant retention, CGM use, and treatment group adherence. It was completed by 142 CGM participants and by 75 CGM + BGM participants. All participants were using CGM until the 6th month with the average use of 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively. Also, BGM tests from meter downloads, including the two required daily BGM tests (CGM calibration), averaged 2.8 ± 0.9 in the CGM and 5.4 ± 1.4 in the CGM + BGM groups, respectively (P < 0.001). Mean time of 70-180 mg/dL spent was 63 ±13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group with 0% adjusted difference and one-sided 95% CI – 2%. No severe hypoglycemic events occurred in the CGM-only group; one occurred in the CGM+BGM group; and no DKA occurred in either group.
In conclusion, use of CGM alone without regular use of confirmatory BGM was shown as safe and effective as using CGM + BGM in well-controlled adults with T1D at low risk for severe hypoglycemia. All other efficacy outcomes for measured HbA1c, hyper/hypoglycemia, and glucose variability results in the CGM only and CGM + BGM groups were identical. Results were comparable between experienced CGM users and CGM naïve participants, between older versus younger subjects, and between participants with higher and lower education levels. The major limitation was generalizability of the results based on inclusion criteria with adults with T1D who used an insulin pump and had a well controlled mean HbA1c 7.0% with adherence to the study protocol and excluded individuals with significant hypoglycemia unawareness or a substantial amount of CGM-measured hypoglycemia. It seemed rational to apply the results to individuals who fit the study profile and use multiple insulin injections daily because the impact of sensor inaccuracy in determining the amount of a bolus should be similar in pump and injection users. However, further studies are required to assess the safety of CGM without routine BGM in individuals with higher HbA1c levels, who perform BGM <4 times a day, and with hypoglycemia unawareness. Overall, the clinical application of CGM alone can benefit T1D patients by reducing the burden of multiple daily fingersticks and enhance the cost-effectiveness by reducing the number of daily BGM test strips.
- In well-controlled adults with T1D meeting the eligibility criteria for this trial, use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with a confirmatory BGM measurement for insulin dosing.
- FDA had expanded the indications for the use of CGM (Dexcom G5 sensor) to replace fingerstick blood glucose testing for diabetes treatment decisions.
- Future studies should include assessment of CGM use without BGM in youth and adults whose diabetes is not well-controlled.
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