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Reference - REPLACE-BG trial (Diabetes Care 2017 Feb 16 early online) (level 3 [lacking direct] evidence)
- Continuous glucose monitoring (CGM) is based on measurements of interstitial fluid glucose and was previously approved by the Food and Drug Administration (FDA) for use only in conjunction with confirmatory blood glucose monitoring (BGM). Approval of the Dexcom G5 Mobile device has been extended to include use in making diabetes treatment decisions without confirmatory BGM.
- In the REPLACE-BG noninferiority trial, 226 adults with well controlled diabetes mellitus type 1 were randomized to CGM with use of confirmatory BGM to make treatment decisions only during prespecified situations (limited) vs. CGM plus use of confirmatory BGM to make all treatment decisions (routine) for 26 weeks.
- The mean proportion of time with CGM-measured glucose in the range of 70-180 mg/dL (3.9-10 mmol/L) over the 26-week period was similar between the groups (63% vs. 65%). The mean number of blood tests performed per day was 2.8 with CGM with limited BGM vs. 5.4 with CGM plus routine BGM (p < 0.001).
Continuous glucose monitoring (CGM) sensors placed under the skin transmit tissue fluid glucose measurements to a wireless monitor, aiding self-management of diabetes. Previously, FDA approval of these monitors was limited to their use as adjuncts to blood glucose monitoring (BGM) (National Institute of Diabetes and Digestive and Kidney Diseases). As of December 2016, the FDA extended the approval of the Dexcom G5 Mobile Continuous Glucose Monitoring System to allow treatment decisions to be made without routine confirmation by BGM (FDA). The present randomized trial was conducted to evaluate whether CGM with limited BGM is as safe and effective as CGM plus routine BGM to make decisions regarding glycemic control. The CGM device used in this trial is the Dexcom G4 Platinum CGM System (Software 505). In this noninferiority trial, 226 adults (mean age 44 years) with type 1 diabetes with a hemoglobin A1c value ≤ 9%, using an insulin pump, with a demonstrated willingness and ability to use CGM and BGM in a pretrial phase, and with a low risk of hypoglycemia were randomized 2:1 to CGM with use of confirmatory BGM to make treatment decisions only during prespecified situations (limited) vs. CGM plus use of confirmatory BGM to make all treatment decisions (routine) for 26 weeks. Patients with > 10% of CGM glucose concentrations< 60 mg/dL (3.3 mmol/L) during the pretrial phase were not enrolled. All patients were instructed to perform 2 BGMs per day to calibrate the continuous monitor and to perform BGM if CGM-measured glucose concentrations were > 300 mg/dL (16.7 mmol/L). Patients in the CGM with limited BGM group were also told to perform BGM for several specific situations, such as rapidly changing CGM readings, hypoglycemia symptoms with discrepant CGM readings, treatment of hypoglycemia without rising CGM readings, hyperglycemia > 250 mg/dL (13.9 mmol/L), on sick days, or for four hours after taking acetaminophen. Patients in the CGM plus routine BGM group were also told to perform BGM whenever an insulin bolus was given, when treating or preventing hypoglycemia, and before bedtime. The primary outcome was the proportion of time with CGM-measured glucose in the range of 70-180 mg/dL (3.9-10 mmol/L) over the 26-week period. CGM with limited BGM was considered to be noninferior if the primary outcome was < 7.5% lower at the limit of a 1-sided 95% confidence interval than with CGM plus routine BGM.
The primary outcome was 63% with CGM with limited BGM vs. 65% with CGM plus routine BGM (adjusted difference 0%, 1-sided limit of 95% CI -2%), establishing noninferiority for CGM with limited BGM. Among the 96% of patients completing the trial, the mean BGMs per day including the two required for CGM calibration was 2.8 with CGM with limited BGM vs. 5.4 with CGM plus routine BGM (p < 0.001). None of the patients had diabetic ketoacidosis and there was 1 hypoglycemic event requiring assistance in the CGM plus routine BGM group.
The REPLACE-BG trial demonstrated that CGM with limited BGM was not associated with increased risk of diabetic ketoacidosis or severe hypoglycemic events and had similar glycemic control compared to CGM with routine BGM. The conditions under which these results were obtained included a compliant patient population at low risk for hypoglycemia and the use of BGM confirmation for specific situations in addition to the two daily calibration blood glucose measurements. Overall, these data suggest that CGM with BGM for prespecified conditions may allow for a lower number of daily blood glucose measurements than routinely used and safe glycemic management in selected, well-controlled adults with diabetes mellitus type 1.
For more information, see the topics Glycemic control monitoring and Diabetes mellitus type 1 in DynaMed Plus. DynaMed users click here.