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While drawing together what is currently known regarding this topic, the future direction in this field and clinical implications posed by polypharmacy on CGM performance are considered. This first in a series of four review articles classifies commercially available CGMs by glucose measurement principle before reviewing what is currently known regarding substance interference mechanisms and design approaches that may serve to reduce interfering effects. Points covered include the following: minimally invasive electrochemical CGMs, which may be classified by first-, second-, or third-generational design (these models are at risk of interference from electroactive substances, or substances that can interfere with the enzymatic biorecognition process); non-invasive fluid sampling CGMs, which draw glucose across the skin barrier but are similarly reliant on the electrochemical measurement of an enzymatic reaction product; and minimally invasive implantable CGMs, which exhibit different interfering substance behaviors to other CGM classes, using a non-enzyme-based glucose-recognition agent coupled to optical detection. An understanding of substance-interfering mechanisms allows consideration of the potential impact on clinical accuracy of substances that are routinely prescribed, can be purchased over the counter, or are new to market.<\/jats:p>","DOI":"10.1177\/19322968251377027","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T08:20:27Z","timestamp":1762849227000},"page":"1671-1683","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of Interfering Substances on Continuous Glucose Monitors: Part 1: Classification of Continuous Glucose Monitoring Devices and Mechanisms of Substance Interference"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1983-0461","authenticated-orcid":false,"given":"Steven John","family":"Setford","sequence":"first","affiliation":[{"name":"LifeScan Scotland Ltd., Inverness, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/19322968211065065"},{"key":"e_1_3_3_3_2","unstructured":"Food and Drug Administration. 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