Evaluation of Accuracy and Safety of the Next-Generation Up to 180-Day Long-Term Implantable Eversense Continuous Glucose Monitoring System: The PROMISE Study.

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.

A Prospective Multicenter Evaluation of the Accuracy of a Novel Implanted Continuous Glucose Sensor: PRECISE II.

BACKGROUND: Persistent use of real-time continuous glucose monitoring (CGM) improves diabetes control in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS: PRECISE II was a nonrandomized, blinded, prospective, single-arm, multicenter study that evaluated the accuracy and safety of the implantable Eversense CGM system among adult participants with T1D and T2D (NCT02647905). The primary endpoint was the mean absolute relative difference (MARD) between paired Eversense and Yellow Springs Instrument (YSI) reference measurements through 90 days postinsertion for reference glucose values from 40 to 400 mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor longevity. The primary safety endpoint was the incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days postinsertion. RESULTS: Ninety participants received the CGM system. The overall MARD value against reference glucose values was 8.8% (95% confidence interval: 8.1%-9.3%), which was significantly lower than the prespecified 20% performance goal for accuracy (P < 0.0001). Ninety-three percent of CGM values were within 20/20% of reference values over the total glucose range of 40-400 mg/dL. Clarke Error Grid analysis showed 99.3% of samples in the clinically acceptable error zones A (92.8%) and B (6.5%). Ninety-one percent of sensors were functional through day 90. One related SAE (1.1%) occurred during the study for removal of a sensor. CONCLUSIONS: The PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings through the intended 90-day sensor life with a favorable safety profile.

Thiazolidinediones, peripheral edema, and type 2 diabetes: incidence, pathophysiology, and clinical implications.

OBJECTIVE: To present an objective, evidence-based review of edema associated with thiazolidinedione use in patients with type 2 diabetes. METHODS: We review the incidence, pathophysiology, and clinical significance of edema associated with the use of thiazolidinediones, with specific emphasis on the two currently available thiazolidinediones, rosiglitazone and pioglitazone. RESULTS: Both pioglitazone and rosiglitazone have been associated with increased development of edema in clinical trials. The incidence of edema in these trials varies from about 3.0 to 7.5% with the thiazolidinediones compared with 1.0 to 2.5% with placebo or other oral antidiabetic therapy. The highest incidence of edema has been reported when thiazolidinediones are used in combination with insulin. In clinical studies, these patients have an incidence of edema of 15.3% when treated with insulin plus pioglitazone and 14.7% when treated with insulin plus rosiglitazone (compared with 7.0% and 5.4% in the insulin-only groups, respectively). In addition to peripheral edema, reports have described pulmonary edema associated with thiazolidinedione therapy. In all such reports, patients failed to respond to diuretics during use of thiazolidinediones. Clinical improvement ensued only after discontinuation of thiazolidinedione therapy. Therefore, thiazolidinediones either may have some effect on the delivery of diuretics to the lumen of the nephron or may induce tubular alterations that impair the ability of the nephrons to respond to diuretics. Several potential causes have been postulated to precipitate edema in patients with diabetes who are treated with these agents: increased plasma volume, increased renal sodium reabsorption, reflex sympathetic activation, alteration of intestinal ion transport, and increased production of vascular endothelial growth factor. CONCLUSION: Available evidence suggests that edema is a class effect of the thiazolidinediones and is multifactorial in origin. Thiazolidinedione-associated edema seems to be dose related and occurs most frequently when thiazolidinediones are used in combination with insulin. Hence, therapy with these agents should be initiated at low doses, and patients should undergo assessment for edema and congestive heart failure during the first few weeks of treatment. Caution should be exercised when thiazolidine-diones are used in those at risk for or with a history of heart failure. Options for management thiazolidinedione-associated edema include dose reduction, drug discontinuation, and symptomatic therapy with diuretics. Further studies are needed to elucidate the mechanisms responsible for the cause of edema in patients with type 2 diabetes treated with thiazolidinediones and to determine whether certain factors might predict susceptibility to development of edema and congestive heart failure.