Assessing non-adjunctive CGM safety at home and in new markets (ANSHIN).

INTRODUCTION: Continuous glucose monitoring (CGM) can guide treatment for people with type 1 (T1D) and type 2 diabetes (T2D). The ANSHIN study assessed the impact of non-adjunctive CGM use in adults with diabetes using intensive insulin therapy (IIT). MATERIALS AND METHODS: This single-arm, prospective, interventional study enrolled adults with T1D or T2D who had not used CGM in the prior 6 months. Participants wore blinded CGMs (Dexcom G6) during a 20-day run-in phase, with treatment based on fingerstick glucose values, followed by a 16-week intervention phase and then a randomized 12-week extension phase with treatment based on CGM values. The primary outcome was change in HbA1c. Secondary outcomes were CGM metrics. Safety endpoints were the number of severe hypoglycaemic (SH) and diabetic ketoacidosis (DKA) events. RESULTS: Of the 77 adults enrolled, 63 completed the study. Those enrolled had mean (SD) baseline HbA1c of 9.8% (1.9%), 36% had T1D, and 44% were ≥65 years old. Mean HbA1c decreased by 1.3, 1.0 and 1.0 percentage points for participants with T1D, T2D or age ≥65, respectively (p < .001 for each). CGM-based metrics including time in range also improved significantly. SH events decreased from the run-in period (67.3 per 100 person-years) to the intervention period (17.0 per 100 person-years). Three DKA events unrelated to CGM use occurred during the total intervention period. CONCLUSIONS: Non-adjunctive use of the Dexcom G6 CGM system improved glycaemic control and was safe for adults using IIT.

Comparisons of Fifth-, Sixth-, and Seventh-Generation Continuous Glucose Monitoring Systems.

BACKGROUND: Between-system differences for continuous glucose monitoring (CGM) devices have important clinical consequences. PURPOSE: Here we review attributes of Dexcom's fifth-, sixth-, and seventh-generation (G5, G6, and G7) CGM systems. METHODS: Accuracy metrics were derived from preapproval trials of the three systems and compared after propensity score adjustments were used to balance baseline demographic characteristics. Metrics included mean absolute relative differences (MARD) between CGM and YSI values and the proportion of CGM values within 20% or 20 mg/dL of the YSI values ("%20/20"). Ease-of-use was evaluated by formal task analysis. CONCLUSIONS: Adjusted MARD and %20/20 agreement rates were 9.0%/93.1% (abdomen-placed G5), 9.9%/92.3% (abdomen-placed G6), 9.1%/93.2% (abdomen-placed G7), and 8.2%/95.3% (arm-placed G7). Task analysis favored G7 over earlier systems. Favorable clinical outcomes such as hemoglobin A1c reduction and hypoglycemia avoidance seen with G5 and G6 are anticipated with G7 use.

Accuracy and Safety of Dexcom G7 Continuous Glucose Monitoring in Adults with Diabetes.

Background: We evaluated the accuracy and safety of a seventh generation (G7) Dexcom continuous glucose monitor (CGM) during 10.5 days of use in adults with diabetes. Methods: Adults with either type 1 or type 2 diabetes (on intensive insulin therapy or not) participated at 12 investigational sites in the United States. In-clinic visits were conducted on days 1 or 2, 4 or 7, and on the second half of day 10 or the first half of day 11 for frequent comparisons with comparator blood glucose measurements obtained with the YSI 2300 Stat Plus glucose analyzer. Participants wore sensors concurrently on the upper arm and abdomen. Accuracy evaluation included the proportion of CGM values within 15% of comparator glucose levels >100 mg/dL or within 15 mg/dL of comparator levels ≤100 mg/dL (%15/15), along with the %20/20 and %30/30 agreement rates. The mean absolute relative difference (MARD) between temporally matched CGM and comparator values was also calculated. Results: Data from 316 participants (619 sensors, 77,774 matched pairs) were analyzed. For arm- and abdomen-placed sensors, overall MARDs were 8.2% and 9.1%, respectively. Overall %15/15, %20/20, and %30/30 agreement rates were 89.6%, 95.3%, and 98.8% for arm-placed sensors and were 85.5%, 93.2%, and 98.1% for abdomen-placed sensors. Across days of wear, glucose concentration ranges, and rates of change, %20/20 agreement rates varied by no more than 9% from the overall %20/20. No serious adverse events were reported. Conclusions: The G7 CGM provides accurate glucose readings with single-digit MARD with arm or abdomen placement in adults with diabetes. Clinicaltrials.gov: NCT04794478.

Mitigation of Rebound Hyperglycemia With Real-Time Continuous Glucose Monitoring Data and Predictive Alerts.

BACKGROUND: Excess carbohydrate intake during hypoglycemia can lead to rebound hyperglycemia (RH). We investigated associations between RH and use of real-time continuous glucose monitoring (rtCGM) and an rtCGM system's predictive alert. METHODS: RH events were series of sensor glucose values (SGVs) >180 mg/dL starting within two hours of an antecedent SGV <70 mg/dL. Events were characterized by their frequency, duration (consecutive SGVs >180 mg/dL × five minutes), and severity (area under the glucose concentration-time curve). To assess the impact of rtCGM, data gathered during the four-week baseline phase (without rtCGM) and four-week follow-up phase (with rtCGM) from 75 participants in the HypoDE clinical trial (NCT02671968) of hypoglycemia-unaware individuals were compared. To assess the impact of predictive alerts, we identified a convenience sample of 24 518 users of an rtCGM system without predictive alerts who transitioned to a system whose predictive alert signals an SGV ≤55 mg/dL within 20 minutes (Dexcom G5 and G6, respectively). RH events from periods of blinded versus unblinded rtCGM wear and from periods of G5 and G6 wear were compared with paired t tests. RESULTS: Compared to RH events in the HypoDE baseline phase, the mean frequency, duration, and severity of events fell by 14%, 12%, and 23%, respectively, in the follow-up phase (all P < .05). Compared to RH events during G5 use, the mean frequency, duration, and severity of events fell by 7%, 8%, and 13%, respectively, during G6 use (all P < .001). CONCLUSIONS: Rebound hypreglycemia can be objectively quantified and mitigated with rtCGM and rtCGM-based predictive alerts.

Sustainable Use of a Real-Time Continuous Glucose Monitoring System from 2018 to 2020.

We aimed to describe patterns of continuous glucose monitoring (CGM) system use and glycemic outcomes from 2018 to 2020 in a large real-world cohort by analyzing anonymized data from US-based CGM users who transitioned from the G5 to the G6 System (Dexcom) in 2018. The main end points were persistent use, within-day and between-day utilization, hypoglycemia, time in range (TIR, 70-180 mg/dL [3.9-10 mmol/L]), and use of the optional calibration feature in 2019 and 2020. In a cohort of 31,034 individuals, rates of persistent use were high, with 27,932 (90.0%) and 26,861 (86.6%) continuing to upload data in 2019 and 2020, respectively. Compared with G5 use, G6 use was associated with higher device utilization, less hypoglycemia, higher TIR (in 2020), and >80% fewer calibrations in both 2019 and 2020 (P's < 0.001). High persistence and utilization of the G6 system may contribute to sustainable glycemic outcomes and decreased user burden.

Real-Time Continuous Glucose Monitoring During the Coronavirus Disease 2019 Pandemic and Its Impact on Time in Range.

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted the lives of people with diabetes. Use of real-time continuous glucose monitoring (rtCGM) helped manage diabetes effectively. Some of these disruptions may be reflected in population-scale changes to metrics of glycemic control, such as time-in-range (TIR). Methods: We examined data from 65,067 U.S.-based users of the G6 rtCGM System (Dexcom, Inc., San Diego, CA) who had uploaded data before and during the COVID-19 pandemic. Users associated with three counties that included the cities of Los Angeles, Chicago, and New York or with five regions designated by the Centers for Disease Control and Prevention (CDC) were compared. Public data were used to associate regions with prepandemic and intrapandemic glycemic parameters, COVID-19 mortality, and median household income. Results: Compared with an 8-week prepandemic interval before stay-at-home orders (January 6, 2020, to March 1, 2020), overall mean (standard deviation) TIR improved from 59.0 (20.1)% to 61.0 (20.4)% during the early pandemic period (April 20, 2020 to June 14, 2020, P < 0.001). TIR improvements were noted in all three counties and in all five CDC-designated regions. Higher COVID-19 mortality was associated with higher proportions of individuals experiencing TIR improvements of ≥5 percentage points. Users in economically wealthier zip codes had higher pre- and intrapandemic TIR values and greater relative improvements in TIR. TIR and pandemic-related improvements in TIR varied across CDC-designated regions. Conclusions: Population-level rtCGM data may be used to monitor changes in glycemic control with temporal and geographic specificity. The COVID-19 pandemic is associated with improvements in TIR, which were not evenly distributed across the United States.

Safety and Functional Integrity of Continuous Glucose Monitoring Components After Simulated Radiologic Procedures.

BACKGROUND: We investigated wearable components of the Dexcom G6 continuous glucose monitoring (CGM) System in simulated therapeutic and diagnostic radiologic procedures. METHODS: G6 transmitters were loaded with simulated glucose data and attached to sensors. Sets of sensor/transmitter pairs were exposed to x-rays to simulate a radiotherapeutic procedure and to radiofrequency (RF) and magnetic fields to simulate diagnostic magnetic resonance imaging (MRI). The x-ray simulation provided a cumulative dose of 80 Gy. The MRI simulation used RF fields oscillating at 64 or 128 MHz and magnetic fields of 1.5 or 3 T. During the MRI simulation, displacement force, induced heating, and induced currents were measured. After the simulations, bench tests were used to assess data integrity on the transmitters and responsiveness of sensors to various concentrations of aqueous glucose. RESULTS: Glucose concentrations reported by sensor/transmitter pairs after undergoing x-irradiation or a simulated MRI exam were similar to those from control (unexposed) devices. During the 3 T MRI simulation, the devices experienced a displacement force of 306 g, which was insufficient to dislodge the sensor/transmitter from the substrate, RF-induced heating of <2°C, and an induced current of <16 pA. Data stored on the transmitters prior to the MRI simulation remained intact. CONCLUSION: Wearable components of the G6 CGM System retain basic functionality and data integrity after exposure to simulated therapeutic and diagnostic radiologic procedures. The devices are unlikely to be affected by x-irradiation used in typical imaging studies. Simulated MRI procedures create displacement force, minimal heating, and current in sensor/transmitter pairs.

Real-World Hypoglycemia Avoidance With a Predictive Low Glucose Alert Does Not Depend on Frequent Screen Views.

BACKGROUND: Frequent real-time continuous glucose monitoring (rtCGM) data viewing has been associated with reduced mean glucose and frequent scanning of an intermittently scanned continuous glucose monitoring (isCGM) system has been associated with reduced hypoglycemia for patients with diabetes. However, requiring patients to frequently interact with their glucose monitoring devices to detect actual or impending hypoglycemia is burdensome. We hypothesized that a predictive low glucose alert, which forecasts glucose ≤55 mg/dL within 20 minutes and is included in a new rtCGM system, could mitigate hypoglycemia without requiring frequent device interaction. METHODS: We analyzed estimated glucose values (EGVs) from an anonymized convenience sample of 15,000 patients who used Dexcom G6 (Dexcom, Inc, San Diego, CA, USA) and its mobile app for at least 30 days with or without the "Urgent Low Soon" alert (ULS) enabled. Screen view frequency was determined as the frequency with which the trend screen was accessed on the app. Multiple screen views within any 5-minute interval were counted as one. Hypoglycemia exposure for patients in the top and bottom quartiles of screen view frequency (>8.25 and <3.30 per day, respectively) was calculated as the percentage of EGVs below various thresholds. RESULTS: Over 93% of users enabled the ULS alert; its use was associated with significantly reduced hypoglycemia <55 and <70 mg/dL, independent of screen view frequency. CONCLUSION: Use of the G6 ULS alert may disencumber rtCGM users by promoting significant reductions in hypoglycemia without requiring frequent device interactions.

Real-World Hypoglycemia Avoidance with a Continuous Glucose Monitoring System's Predictive Low Glucose Alert.

BACKGROUND: Programmable and fixed auditory and/or vibratory threshold alerts are essential features of real-time continuous glucose monitoring (rtCGM) systems that provide users time to intervene before the onset of clinical hypoglycemia or hyperglycemia. A sixth-generation rtCGM system from Dexcom, Inc. (G6) includes a new alert that is triggered when an algorithm predicts that an estimated glucose value ≤55 mg/dL will occur within 20 min, allowing users more time to act to avoid hypoglycemia. We examined whether this predictive low glucose alert provided added benefit to traditional low threshold alerts. METHODS: We analyzed glucose values from an anonymized sample of 1424 patients who transitioned to G6 from the preceding fifth-generation system (G5) with no predictive alert. Users with the low threshold alert setting of 70 or 80 mg/dL were evaluated separately. Receiver users, those who disabled the predictive low glucose alert, or those with <30 days of data immediately before or after the transition to G6 were excluded. RESULTS: Percent time <54, ≤55, <70, and >250 mg/dL fell significantly after the transition to G6, independent of low threshold alert setting. Time in range improved for G6 users with a low threshold alert setting of 70 mg/dL. CONCLUSIONS: Advance warning provided by predictive low glucose alerts may further reduce hypoglycemia among rtCGM-experienced users.

Real-Time Sharing and Following of Continuous Glucose Monitoring Data in Youth.

BACKGROUND: Those caring for children and adolescents with diabetes often use glucose concentration and trending information in management decisions. Some continuous glucose monitoring (CGM) systems offer real-time sharing and monitoring capabilities through mobile apps carried by the person with diabetes and the caregiver(s), respectively. Few large studies have explored real-world associations between sharing and following, CGM utilization, and glycemic outcomes. METHODS: We performed a retrospective evaluation of device usage and glycemic control in 15,000 youth ranging in age from 2 to 18 years by analyzing anonymized data that had been uploaded with a mobile app that provides optional sharing. The presence or absence of a real-time monitor (a "Follower") was established on 15 June 2018. Each day with ≥ 1 uploaded glucose values was counted as a day of device usage. Between-group glucose comparisons were made with two-sided Welch's t tests. RESULTS: Overall, 94.8% of the population used the sharing feature and had at least one Follower. The mean numbers of Followers for patients aged 2-5, 6-12, and 13-18 years were 2.8, 2.8, and 2.4, respectively. In all three age categories, the presence of at least one Follower was associated with lower mean glucose values, more glucose values in the 70- to 180-mg/dL range, correspondingly fewer glucose values representing hypoglycemia and hyperglycemia, and significantly more device utilization. CONCLUSION: Real-time sharing and following of CGM data are associated with improved device utilization and glycemic parameters. The observed association suggests either more timely interventions or higher levels of engagement among the caregivers or the youth with diabetes. FUNDING: Dexcom, Inc.

Accuracy, Utilization, and Effectiveness Comparisons of Different Continuous Glucose Monitoring Systems.

BACKGROUND: Accuracy and feature sets of continuous glucose monitoring (CGM) systems may influence device utilization and outcomes. We compared clinical trial accuracy and real-world utilization and effectiveness of two different CGM systems. MATERIALS AND METHODS: Separately conducted accuracy studies of a fifth-generation and a sixth-generation CGM system involved 50 and 159 adults, respectively. For between-system performance comparisons, propensity score methods were utilized to balance cohort characteristics. Real-world outcomes were assessed in 10,000 anonymized patients who had switched from the fifth-generation to the sixth-generation system and had used connected mobile devices to upload data from both systems, allowing pairwise comparisons of device utilization and glucose concentration distributions. RESULTS: Propensity score-adjusted mean absolute relative differences for the fifth- and sixth-generation systems were 9.0% and 9.9%, and the percentages of values within ±20%/20 mg/dL were 93.1% and 92.5%, respectively. The sixth-generation system, but not the fifth-generation system, met accuracy criteria for interoperable CGM systems. Both systems had high real-world utilization rates (93.8% and 95.3% in the fifth- and sixth-generation systems, respectively). Use of the sixth-generation system was associated with fewer glucose values <55 mg/dL (<3.1 mmol/L) (0.7% vs. 1.1%, P < 0.001) and more values 70-180 mg/dL (3.9-10.0 mmol/L) (57.3% vs. 56.0%, P < 0.001) than the fifth-generation system. CONCLUSIONS: CGM performance outcomes can be compared through the propensity score analysis of clinical trial data and pairwise comparisons of real-world data. The systems compared here had nearly equivalent accuracy and utilization rates. Longer term biochemical and psychosocial benefits observed with the fifth-generation system are also expected with the sixth-generation system.

Performance of a Factory-Calibrated, Real-Time Continuous Glucose Monitoring System in Pediatric Participants With Type 1 Diabetes.

BACKGROUND: The perceived value and consistent use of continuous glucose monitoring (CGM) systems depends in part on their accuracy. We assessed the performance of a sixth-generation CGM system (Dexcom G6) in children and adolescents. METHODS: Forty-nine participants (6-17 years of age, mean ± SD of 13.5 ± 3.3 years), all with type 1 diabetes, enrolled and data were available from 37. Each participant wore 1 sensor for up to 10 days and was asked to undergo an in-clinic visit lasting 6-12 hours for frequent blood glucose (BG) sample testing on one of the sensor wear days. Estimated glucose values (EGVs) from the G6 system were compared with venous BG values measured with a laboratory reference instrument (YSI). RESULTS: The overall mean absolute relative difference (MARD) for 1387 EGV-YSI pairs was 7.7%, and the overall percentage of EGVs within 20% or 20 mg/dL of the YSI reference value (for YSI > or ⩽100 mg/dL, respectively, the "%20/20") was 96.2%. The %20/20 was 92.1% on Day 1 and 91.0% on Day 10 of sensor wear. For EGVs <70 mg/dL, 92.6% of the YSI values were within 20 mg/dL and for EGVs >250 mg/dL, 100% of the YSI values were within 20%. Differences between EGVs and YSI values in over 99.9% of the pairs posed no or only slight clinical risk as evaluated by surveillance error grid analysis. CONCLUSIONS: The accuracy of the G6 CGM system in pediatrics may encourage consistent use of the system and contribute to improved glycemic outcomes in this population.

The Effect of Reduced Self-Monitored Blood Glucose Testing After Adoption of Continuous Glucose Monitoring on Hemoglobin A1c and Time in Range.

The effectiveness of real-time continuous glucose monitoring (rtCGM) in adults with diabetes treated with insulin injections was evaluated in the 24-week DIAMOND clinical trial comparing rtCGM users to a control group using self-monitored blood glucose (SMBG) testing ( Clinicaltrials.gov : NCT02282397). All participants were instructed to use SMBG results for diabetes management decisions; however, SMBG testing frequency varied within the rtCGM group. This brief report evaluated how SMBG frequency changes in the rtCGM group were correlated with glycemic outcomes in the same trial. Baseline and end-of-study hemoglobin A1c (HbA1c) levels, percentages of CGM values in the 70-180 mg/dL target range (time in range [TIR]), mean of daily differences (MODD), and glycemic coefficients of variation (CVs) were compared. The rtCGM group analyzed included 175 participants-99 with type 1 diabetes (T1D) and 76 with type 2 diabetes (T2D). When comparing participants whose SMBG testing frequency decreased by >1/day versus ≤1/day, mean change in HbA1c was similar (-0.9 ± 0.7 percentage points in both groups, P = 0.59), as was change in TIR (+3.9 ± 14.3 vs. +5.7 ± 13.7 percentage points, respectively, P = 0.39). Likewise, when comparing participants in the highest and lowest quartiles of SMBG frequency reduction (≥2.2 vs. ≤0.4 fewer tests/day, respectively), changes in HbA1c (-0.8 ± 0.6 vs. -0.9 ± 0.6 percentage points, respectively, P = 0.52) and TIR (+4.8 ± 13.2 vs. +5.6 ± 12.7 percentage points, respectively, P = 0.98) were similar. The mean (standard deviation [SD]) change in MODD was -8.3 mg/dL (14.8) and -5.5 mg/dL (14.7) for participants who reduced their SMBG frequency by >1 test/day and ≤1 test/day, respectively; the mean (SD) change in CV was -3.6% (5.0) and -1.6% (5.1) for participants who reduced their SMBG frequency by >1 test/day and ≤1 test/day, respectively. These findings suggest that individuals who decrease the frequency of SMBG testing can effectively base some of their diabetes-related treatment decisions on glucose concentrations, trend information, and alarms provided by their rtCGM systems.

Manufacturing Process Changes and Reduced Skin Irritations of an Adhesive Patch Used for Continuous Glucose Monitoring Devices.

Adhesives used for continuous glucose monitoring (CGM) devices can cause skin irritations, which sometimes lead to abandonment of the therapy. A previous sensor manufacturing process involved two separate adhesives-one applied to the skin-facing surface of the fabric patch, and a second, ethyl cyanoacrylate-based adhesive, which secured the plastic transmitter housing to the superficial side of the patch. Our current process for attaching the transmitter housing to the fabric patch uses heatstaking, wherein the housing is heated and pressed against the patch with a specialized assembly apparatus. Heatstaking simplifies the sensor assembly process and obviates the need for the second adhesive, which may lead to lower risk of skin irritation(s) in some patients.