Lifecare ASA

Regulatory Filings • Mar 6, 2024

DYNAMIC INTERFERENCE TESTING RESULTS WITH THE LIBRE 3 CONTINUOUS GLUCOSE MONITORING DEVICE IN COMPARISON TO LIBRE 2

Background

Little is known regarding the potential interference of drugs or nutritional substances on commercially available CGM sensors. We have developed an in-vitro test method to continuously and dynamically investigate potential interferents. Previously, we have identified 11 substances (from a panel of 68) that influenced the Libre2 sensor in a previous experiment. Here, we report on the test results with the complete panel when testing the Libre3 and Libre 2sensors in parallel.

Results

Interference (bias at the highest concentration tested from baseline, L2/L3) was seen with the following substances: xylose: 178%/94%, galactose: 134%/83%, mannose: 130%/88%, hydroxyurea 84%/137%, ascorbic acid 48%/49%, dithiothreitol 46%/51%, methyldopa 16%/20%, ibuprofen 14%/11%, red wine 12%/14% (corrected for YSI glucose changes), N-acetyl-cysteine: 11%/20%, and icodextrin: 10%/9%. No interference was seen with the other substances. In contrast to L2, Libre 3 sensors were also influenced by L-dopa (7 % vs 14%).

The Libre 3 sensor showed the same interference pattern as previously found with Libre 2 indicating similar performance. As highlighted by the unexpected in vitro interference effect observed with hydroxyurea on the L2 and L3 systems, the clinical relevance of our findings for routine care should now best be investigated in people with diabetes.

Methods

We have developd a laboratory test method and protocol for dynamic interference testing (Pfützner et al, 2024). Three sensors from each type were exposed to substance gradients from zero to supraphysiological concentrations generated by HPLC-pumps at a stable glucose concentration of 200 mg/dL (reference method: YSI Stat2300Plus). Interference was assumed if the CGM needle sensors showed a mean bias >10% from baseline with a tested substance at any given substance concentration.

Pfützner A., Jensch H., Setford S., Kuhl C., Weingärtner L., Grady M., Holt E., Thomé N., Mainz, Germany; Inverness, UK, Malvern, PA, Wiltz, Luxembourg; Bergen, Norway

Fig.1: Dynamic interference test for CGM sensors Fig.2 Libre 2 & 3 interference by 12/10 substances Table 1. Interfering substances

Reference:

Pfützner A, Jensch H, Cardinal C, Srikanthamoorthy G, Riehn E, Thomé N. Laboratory Protocol and Pilot Results for Dynamic Interference Testing of Continuous Glucose Monitoring Sensors. J Diabetes Sci Technol. 2022:19322968221095573. (epub ahead of print) doi: 10.1177/19322968221095573. PMID: 35549522.

Acknowledgements: This project received financial support from the European Union's Horizon 2020 research and innovation program under grant agreement No 951933 (ForgetDiabetes) and also from LifeScan Global Corporation, Malvern, PA, USA..

Substance	Maximum Concentration tested	Bias over Baseline		Type of substance
		L2	L3
Ascorbic Acid	6 mg/dL	+48%	+49%	nutrient
Dithiothreitol	6 mg/dL	+46%	+51%	drug
Galactose	300 mg/dL	+134%	+83%	nutrient
Hydroxyurea	9.12 mg/dL	+84%	+137%	drug
Ibuprofen	50 mg/dL	+14%	-	drug
Icodextrine	224 mg/dL	+10%	-	nutrient, drug
L-Dopa	0,75 mg/dL	+7%	+14%	drug
Mannose	300 mg/dL	+130%	+88%	sugar alcohol
Methyldopa	2 mg/dL	+16%	+20%	drug
N-Acetyl-cysteine	55.4 mg/dL	+11%	+20%	Drug
Red wine	3.8 mL/dL	+12%*	+13%	nutrient
Xylose	300 mg/dL	+178%	+102%	nutrient
*red wine contained 10mg/dL glucose; BOB is adjusted for the reference reading