Katherine S. Tweden

The implanted Eversense Continuous Glucose Monitoring (CGM) System transitioned from 90- to 180- to 365-day durations marketed today. This report summarizes the 365-day clinical study. ENHANCE was a prospective, multicenter study evaluating the accuracy and safety of the Eversense 365 CGM system through 1 year in adults with diabetes. Accuracy and adverse events (AEs) were assessed during 14 in-clinic visits comparing CGM and Yellow Springs Instrument reference glucose measurements, including during hyperglycemia and hypoglycemia challenges. In total, 110 participants were implanted with the Eversense 365 CGM System. The overall mean absolute relative difference was 8.8% with primarily one calibration per week. The confirmed alert detection rate at 70 mg/dL was 96.6%, and at 180 mg/dL, it was 97.9%. Ninety percent of the sensors survived 365 days. Interoperable CGM special controls were met. No related serious AEs were reported. The Eversense 365 CGM was shown to be safe and accurate through 1 year with primarily one calibration per week.

Background: Use of continuous glucose monitoring (CGM) systems is being rapidly adopted as standard of care for insulin-requiring patients with diabetes. The PROMISE study (NCT03808376) evaluated the accuracy and safety of the next-generation implantable Eversense CGM system for up to 180 days. Methods: This was a prospective multicenter study involving 181 subjects with diabetes at 8 USA sites. All subjects were inserted with a primary sensor. Ninety-six subjects had a second sensor, either an identical sensor or a modified sensor (sacrificial boronic acid [SBA]), inserted in their other arm (53 and 43 subjects, respectively). Accuracy was evaluated by comparing CGM to YSI 2300 glucose analyzer (Yellow Springs Instrument [YSI]) values during 10 clinic visits (day 1–180). Confirmed event detection rates, calibration stability, sensor survival, and serious adverse events (SAEs) were evaluated. Results: For primary sensors, the percent CGM readings within 20%/20% of YSI values was 92.9%; overall mean absolute relative difference (MARD) was 9.1%. The confirmed alert detection rate at 70 mg/dL was 93% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 56%. Sixty-five percent of the primary sensors survived to 180 days. For the SBA sensors, the percent CGM readings within 20%/20% of YSI values was 93.9%; overall MARD was 8.5%. The confirmed alert detection rate at 70 mg/dL was 94% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 63%. Ninety percent of the SBA sensors survived to 180 days. No device- or insertion/removal procedure-related SAEs were reported. Conclusion: These data show the next-generation Eversense CGM system had sustained accuracy and safety up to 180 days, with an improved calibration scheme and survival, using the primary or SBA sensors.

The Eversense ^® Continuous Glucose Monitoring (CGM) System, with the first long-term, implantable glucose sensor, has been commercially available in Europe and South Africa since 2016 for adults with diabetes. The performance of the sensor over multiple, sequential 90- or 180-day cycles from either real-world experience or clinical studies has not been previously published. The Eversense Data Management System (DMS) was used to evaluate the accuracy of General Data Protection Regulation (GDPR)-compliant sensor glucose (SG) values against self-monitoring of blood glucose (SMBG) from June 2016 through August 2019 among patients with at least four sensor cycles from European and South African health care practices. Mean SG and associated measures of variability, glucose management indicator (GMI), and percent and time in various hypoglycemic, euglycemic, and hyperglycemic ranges were calculated for the 24-h time period over each cycle. In addition, transmitter wear time was evaluated across each sensor wear cycle. Among the 945 users included in the analysis, the mean absolute relative difference (standard deviation [SD]) using 152,206, 174,645, 206,024, and 172,587 calibration matched pairs against SMBG was 11.9% (3.6%), 11.5% (4.0%), 11.8% (4.7%), and 11.5% (4.1%) during the first four sensor cycles, respectively. Mean values of the CGM metrics over the first sensor cycle were 156.5 mg/dL for SG, 54.7 mg/dL for SD, 0.35 for coefficient of variation, and 7.04% for GMI. Percent SG at different glycemic ranges was as follows: 250 mg/dL was 8.1% (117 min). The median transmitter wear time over the first cycle was 83.2%. CGM metrics and wear time were similar over the subsequent three cycles. This real-world evaluation of adult patients with diabetes using the Eversense CGM System in the home setting demonstrated that the implantable sensor provides consistent stable accuracy and CGM metrics over multiple, sequential sensor cycles with no indication of degradation of sensor performance.

Aims: This real‐world study evaluated the changes in glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics associated with use of the implantable 180‐day Eversense CGM System (Eversense) in patients with type 1 diabetes. Materials and methods: This was a prospective, multicentre, observational study among adult participants aged ≥18 years with type 1 diabetes across seven diabetes‐care centres in Italy who had Eversense inserted for the first time. HbA1c was measured at baseline and at 180 days. Changes in time in range [TIR (glucose 70–180 mg/dL)], time above range [TAR (glucose >180 mg/dL)], time below range [TBR (glucose P < 0.0001). As expected, CGM‐naïve patients achieved the greatest reduction in HbA1c (−0.74% ± 0.48%, 8 ± 5 mmol/mol). TIR significantly increased and TAR and mean daily sensor glucose significantly decreased while TBR did not change after 180 days of sensor wear. Conclusions: Real‐world clinical use of the Eversense CGM System for 180 days was associated with significant improvements in HbA1c and CGM metrics among adults with type 1 diabetes. The study is registered on clinicaltrials.gov (NCT04160156).

Previously, the safety and accuracy of the Eversense continuous glucose monitoring (CGM) system were characterized in three pivotal trials among individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) with a single 90- or 180-day sensor insertion–removal cycle. The Post-Market Clinical Follow-up (PMCF) registry is a prospective study evaluating the long-term safety and performance of the Eversense CGM system over multiple sensor insertion–removal cycles among adults with T1D and T2D. All patients who had a sensor subcutaneously implanted across 534 participating centers in Europe and South Africa from June 2016 to August 2018 were enrolled. Adverse events (AEs) were recorded at each visit and patients were instructed to inform their clinic if they experienced any AEs between visits. AEs were adjudicated for relatedness to the device, procedure, or drug (dexamethasone acetate). The primary safety endpoint was the rate of related serious adverse events (SAEs) through four sensor insertion–removal cycles. The registry enrolled 3023 patients. As of last follow-up, 5417 sensors had been inserted with a total of 1260 patient-years (PYs) of follow-up: 969 patients had used the system for at least 6 months and 173 patients had used the system for at least 1 year. No related SAEs were reported. The most frequently reported related AEs were sensor location site infection (0.96%; 2.46 events per 100 PYs), inability to remove the sensor upon first attempt (0.76%; 1.90 events per 100 PYs), and adhesive patch location site irritation (0.66%; 1.59 events per 100 PYs). One nonserious allergic reaction to lidocaine was reported, which resolved with administration of an antihistamine. The full intended sensor life was achieved by 91% of 90-day sensors and 75% of 180-day sensors. The PMCF registry provides real-world evidence that the Eversense CGM system is safe over multiple cycles of use.

Background: A prior study (PRECISE II) demonstrated that an implantable continuous glucose monitoring (CGM) system (Eversense ^® CGM System) provided accurate glucose readings through the 90-day sensor life with a favorable safety profile in participants with type 1 or type 2 diabetes (T1D, T2D). This study was performed to further characterize the accuracy of the system. Methods: PRECISION was a prospective multicenter study that evaluated the accuracy and safety of Eversense among adults with T1D or T2D through 90 days (NCT02647905). Accuracy measures included percentage system agreement and mean absolute relative difference (MARD) between Eversense and Yellow Springs Instrument reference measurements from 40 to 400 mg/dL. The primary safety endpoint was incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days. An updated glucose calculation algorithm was also applied to the sensor data from the PRECISE II study to evaluate consistency of accuracy results. Results: Thirty-five participants received the CGM system. Eighty-five percent of CGM values were within 15/15% of reference and the MARD value against reference was 9.6% (95% confidence interval [CI]: 8.9–10.4). All sensors were functional through day 90. No device- or procedure-related SAEs occurred. Application of the updated algorithm to PRECISE II sensor data resulted in 87% of readings within 15/15% of reference and an MARD value against reference of 8.5% (95% CI: 8.0%–9.1%). Conclusions: PRECISION corroborated prior accuracy and safety findings of the Eversense CGM System through the 90-day sensor life. The updated algorithm improved accuracy of measurements in PRECISE II.

Aim: To investigate the performance of the Eversense XL implantable continuous glucose monitoring (CGM) system through 180 days in a primarily adolescent population with type 1 diabetes (T1D). Materials and methods: This prospective, single‐centre, single‐arm, 180‐day study evaluated the effectiveness and safety of the implantable CGM system in Canadian adolescent and adult subjects with T1D. Accuracy measures included mean absolute relative difference (MARD), 15/15% agreement between CGM glucose and blood glucose measured by Yellow Springs Instruments and surveillance error grid analysis. Adolescent subjects received one sensor in the upper arm and adult subjects received one sensor in each upper arm. In‐clinic CGM system accuracy studies were performed every 30 days. The safety assessment included the incidence of adverse events related to either device or the insertion/removal procedure through 180 days. Results: Thirty‐six subjects (30 adolescent/6 adult, 13 female/23 male, mean age 17 ± 9.2 years, mean body mass index 22 ± 4 kg/m ² ) received the CGM system. Overall MARD was 9.4% (95% CI: 8.6%‐10.5%). CGM system agreement at 15/15% (N = 7163) through 60, 120 and 180 days was 82.9% (95% CI: 78.4%‐86.1%), 83.6% (95% CI: 80.4%‐85.7%) and 83.4% (95% CI: 79.7%‐85.5%), respectively. Surveillance error grid analysis showed 98.4% of paired values in clinically acceptable error zones A and B. No insertion/removal or device‐related serious adverse events were reported. Conclusion: The Eversense XL CGM system is safe and accurate through 180 days in a primarily adolescent population of subjects with T1D.

Background The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes. Methods Participants with body mass index (BMI) 40 to 45 kg/m², or 35 to 40 kg/m² with at least one comorbid condition were randomized to either vBloc therapy or sham intervention for 12 months. After 12 months, participants randomized to vBloc continued open-label vBloc therapy and are the focus of this report. Weight loss, adverse events, comorbid risk factors, and quality of life (QOL) will be assessed for 5 years. Results At 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (−16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (−46 mg/dL), HbA1c (−0.3 %), and systolic (−11 mmHg) and diastolic blood pressures (−10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %. Conclusions vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years. Trial Registration https://clinicaltrials.gov/ct2/show/NCT01327976

Background Vagal nerve blockade (vBloc) therapy was shown to be a safe and effective treatment for moderate to severe obesity. This report summarizes the safety and efficacy of vBloc therapy in the prespecified subgroup of patients with moderate obesity. Methods The ReCharge Trial is a double-blind, randomized controlled clinical trial of participants with body mass index (BMI) of 40–45 or 35–40 kg/m² with at least one obesity-related comorbid condition. Participants were randomized 2:1 to implantation with either a vBloc or sham device with weight management counseling. Eighty-four subjects had moderate obesity (BMI 35–40 kg/m²) at randomization. Results Fifty-three participants were randomized to vBloc and 31 to sham. Qualifying obesity-related comorbidities included dyslipidemia (73 %), hypertension (58 %), sleep apnea (33 %), and type 2 diabetes (8 %). The vBloc group achieved a percentage excess weight loss (%EWL) of 33 % (11 % total weight loss (%TWL)) compared to 19 % EWL (6 % TWL) with sham at 12 months (treatment difference 14 percentage points, 95 % CI, 7–22; p < 0.0001). Common adverse events of vBloc through 12 months were heartburn/dyspepsia and implant site pain; the majority of events were reported as mild or moderate. Conclusions vBloc therapy resulted in significantly greater weight loss than the sham control among participants with moderate obesity and comorbidities with a well-tolerated safety profile.

Background: The VBLOC DM2 study demonstrated that intermittent electrical vagal blocking (vBloc therapy) was safe among subjects with obesity and type 2 diabetes mellitus (DM2) and led to clinically meaningful improvement in weight loss and glycemic parameters at 2 years. Sustainability of these responses at three years is reported here. Methods: VBLOC DM2 is a prospective, observational study of 28 subjects with DM2 and body mass index (BMI) between 30 and 40 kg/m². Safety and changes in weight, glycemic parameters and other risk factors with vBloc therapy are assessed. Mixed models are used to report continuous outcome variables. Results: After three years of therapy, mean percentage of excess weight loss was 21% (95% CI, 14 to 28) or 7% total body weight loss (95% CI, 5 to 9). Hemoglobin A_1c decreased by a mean of 0.6 percentage points (95% CI, 0.2 to 1.0) from a baseline of 7.8%. Fasting plasma glucose declined by a mean of 18 mg/dL (95% CI, 2 to 34) from a baseline of 151 mg/dL. The most common adverse events continued to be heartburn, constipation and neuroregulator site pain which were mostly mild to moderate in severity as noted in earlier reports. Conclusions: Three years of treatment with vBloc therapy resulted in durable improvements in weight loss and glycemic control. vBloc was shown to have favorable safety through 3 years.