The Foreign Body Response (FBR) is the primary biological limitation of Continuous Glucose Monitors (CGMs), preventing them from achieving the indefinite longevity and immediate accuracy of ex vivo test strips. The response occurs in three phases: Protein Adsorption (biofouling), Acute Inflammation (neutrophil attack and oxygen consumption), and Fibrosis (collagen encapsulation).

Crucially, the inflammation phase consumes local oxygen, interfering with Glucose Oxidase (GOx) enzymatic sensors, which causes signal noise during the initial "warm-up" period. Eventually, the formation of an avascular fibrous capsule creates a diffusion barrier, increasing the physiological lag between blood and interstitial fluid glucose until the sensor fails. Manufacturers combat FBR using zwitterionic coatings to resist protein adhesion and drug-eluting membranes (e.g., dexamethasone) to suppress local inflammation, allowing modern sensors to extend functional life from 3 days to 14–180 days.