The majority of CGM systems are designed as electrochemical needle sensors. In principle, they consist of a thin enzyme electrode, mostly coated with the enzyme glucose oxidase (GOD). This is applied to a thin plastic substrate. The size of the flexible electrode is approximately 0.3 × 0.5 mm in cross-section and 5–10 mm in length. Users can insert these small sensors into the subcutaneous fatty tissue themselves with the help of an inserter.
During this process, the sensor electrode is enclosed by a guiding cannula. The small dimensions of the electrode and cannula, along with the quick insertion, ensure that the procedure is very little or not at all painful for the user. The glucose sensor is essentially minimally invasive and measures in the interstitial fluid. It can be thought of as a miniaturized test strip lying in the subcutaneous fat tissue.
Typically, the sensors transmit an average value—calculated over the previous 1 to 5 minutes—to the respective receiving device, often an app on a smartphone. The usage time of transcutaneous CGM sensors ranges between 7 and 15 days. After that, they need to be replaced.
Measurement Using the Enzyme Glucose Oxidase
In the electrochemical CGM systems currently (2025) available on the market, the enzyme glucose oxidase (GOD) is used. In an initial reaction, it converts glucose into gluconolactone and hydrogen peroxide (H₂O₂):
In the subsequent second reaction, the hydrogen peroxide is broken down at an electrode to which an electrical voltage in the millivolt range is applied. As a result, the electrons released generate a small current in the nanoampere range:
Its magnitude increases the more electrons are present (1 nA means that approximately 30 billion glucose molecules were converted per second). The current therefore represents the amount of glucose converted in the tissue area where the glucose sensor is located. Taking the electrode voltage into account, the current flow (shown as ISIG in Fig. SK 5) represents a value for the glucose concentration.
There are modifications to this, for example through the use of a mediator, which reduces the applied electrode voltage and thus minimizes interactions with other components (e.g., in the FreeStyle Libre CGM system from Abbott). This also reduces susceptibility to fluctuations in oxygen concentration in vivo [1]. The use of glucose dehydrogenase (GDH) together with a coenzyme is also possible. Some sensor projects use this enzyme but are not yet available to patients [2].
Fig. SK 5: Schematic representation of an enzymatic glucose sensor in a Medtronic CGM system [3]
The rtCGM systems currently (2025) in predominant use are the Dexcom G6 and G7 from Dexcom, the FreeStyle Libre 3 from Abbott, and the Guardian 4 and Simplera from Medtronic. In addition, CGM systems such as the TouchCare Nano CGM from Medtrum or the Accu-Chek SmartGuide CGM from Roche are available, both based on needle-sensor technology.
A completely different measurement principle is used in the Eversense glucose sensor from Senseonics [4,5]. The small, cylindrical sensor is about the size of half a matchstick. It is implanted into the subcutaneous fatty tissue under local anesthesia. The currently (2025) available Eversense E3 sensor is designed for use up to 180 days; a future system will be usable for up to 365 days before the next implantation is required (including explantation of the old sensor).
The measurement principle is based on fluorescence, meaning that after excitation of a substance, its atoms/molecules release the excitation energy after a short time in the form of electromagnetic waves in the light spectrum. The intensity of the fluorescence signal provides information about the concentration of the molecular components. For this purpose, the outer shell of the glucose sensor consists of a polymer material containing a glucose-binding molecule, a boronate.
This outer cylindrical wall changes its optical properties when loaded with glucose, meaning that the intensity of the fluorescent radiation depends on the concentration of the bound glucose. To measure this, an ultraviolet light-emitting LED is built into the cylinder. When the light hits the boronate, it fluoresces blue-violet. The fluorescent radiation is measured by a photodiode, also located inside the cylinder. The signal is then transmitted from the tissue to a transmitter adhered to the skin and from there sent via Bluetooth to a smartphone.
It is noteworthy that a wide range of additional CGM systems are currently in development—both enzymatic needle sensors and systems based on completely different measurement principles [2]. This also includes non-invasive CGM systems, i.e. systems based solely on physical measurement methods. However, no statements can yet be made regarding their market readiness.
[1] Feldman B, Brazg R, Schwartz S, Weinstein R. A continuous glucose sensor based on wired enzyme technology — results from a 3-day trial in patients with type 1 diabetes. Diabetes Technol Ther. 2003;5(5):769-79. doi: 10.1089/152091503322526978.
[2] Shang T, Zhang JY, Thomas A, Arnold MA, Vetter BN, Heinemann L, Klonoff DC. Products for Monitoring Glucose Levels in the Human Body With Noninvasive Optical, Noninvasive Fluid Sampling, or Minimally Invasive Technologies. J Diabetes Sci Technol. 2022 Jan;16(1):168-214. doi: 10.1177/19322968211007212.
[3] Mastrototaro JJ. The MiniMed Continuous Glucose Monitoring System. Diabetes Technology & Therapeutics. 2000;2(Suppl. 1):S13–S18.
[4] Thomas A, Kolassa R, von Sengbusch S, Danne T. CGM interpretieren: Grundlagen, Technologie, Charakteristik und Konsequenzen des kontinuierlichen Glukosemonitorings. 2nd revised edition. Kirchheim-Verlag 2019; ISBN 978-3-87409-690-694.
[5] Eversense CGM System | Eversense CGM (ascensiadiabetes.com), last accessed: 18.03.2025