Exploratory continuous interstitial glucose monitoring using the FreeStyle Libre 2 device in cynomolgus monkeys

Abstract

Glucose is an important endpoint in efficacy and toxicology assessments for cardiometabolic indications. Collection of serial glucose values can inform treatment-related effects and animal health status. Handling stress can cause heart rate (HR) and glucose spikes in nonhuman primates (NHPs), increasing variability and confounding data interpretation. Continuous glucose monitors (CGMs) are sensor-based systems that provide interstitial glucose (IG) readings without venipuncture; thus reducing handling stress and resultant glucose spikes. The purpose of this study was to evaluate the Freestyle®Libre™2 CGM (FL2-CGMs, Abbott) with NHPs for multiple days with simultaneous continuous HR monitoring and collection of serum to determine glucose and insulin levels at key timepoints. FL2-CGMs were pericutaneously applied to the back of jacketed NHPs for IG measurements. FL2-CGMs retain up to 8 h of data in 15 min increments. IG data were collected at 10 h intervals for 72 h after each dose administration. During phase 1, jacketed external telemetry was used for assessment of concurrent HR over 24 h. Animals were administered saline, oral glucose (1 g/kg) or injections of 0.15 U/kg insulin. Serum glucose and insulin were measured to compare with IG data predose, 8, and 24 h postdose. In phase 2, animals were administered 3 g/kg glucose; IG was monitored over 72 h with repeated serum sampling of glucose and insulin within the first 8 h of data collection to compare magnitude and timing of changes between the two glucose collection methods. Higher IG levels (up to 72 mg/dL above predose levels) were observed with FL2-CGMs in response to 3 g/kg glucose, while changes in IG levels in response to 1 g/kg glucose were not reliably detected outside of observed IG variability. FL2-CGM captured lower glucose levels (12 mg/dL below controls) after administration of 0.15 U/kg insulin. HR spikes due to handling were concurrent with increased glucose (IG and serum) and serum insulin. In conclusion, this investigation demonstrates that FL2-CGMs can be successfully used for characterization of continuous glucose levels in NHPs and provides a significant advantage over glucose measured from serum samples collected from restrained animals.