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Different types of drugs play important roles in controlling diabetes and its complications, but there are some limitations. The glucose-responsive drug delivery system is a novel technology with potential in diabetes treatment. It could automatically release drugs in response to changes in glucose levels in the body to maintain blood glucose within a normal range. The emergence of a glucose-sensitive drug delivery system provides a more intelligent and precise way to treat diabetes. The review is carried out according to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines This review focuses on the recent advances in the drugs and different systems of glucose-sensitive drug delivery, including glucose oxidase, phenylboronic acid, Concanavalin A, and other glucose-reactive systems. Furthermore, the glucose-responsive drug delivery system combined with the application applied in hydrogels, microneedles, and nanoparticles is also explored and summarized. The new platforms to sustain the release of anti-diabetic drugs could be desirable for patients. It could lead to increased adherence and glycemic outcomes for the detection and treatment of diabetes. Furthermore, given the limitations of glucose-responsive drug delivery systems, solutions and perspectives are proposed to help the understanding and application of these systems. This review will be helpful for drug discovery and treatment of diabetes from a new perspective.<\/jats:p>","DOI":"10.3390\/pharmaceutics16101343","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T03:57:09Z","timestamp":1729483029000},"page":"1343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Recent Advances in the Drugs and Glucose-Responsive Drug Delivery Systems for the Treatment of Diabetes: A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Junyu","family":"Liu","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Yi","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiman","family":"Yao","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1097-8822","authenticated-orcid":false,"given":"Pharkphoom","family":"Panichayupakaranant","sequence":"additional","affiliation":[{"name":"Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-9622","authenticated-orcid":false,"given":"Haixia","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e14865","DOI":"10.1111\/dme.14865","article-title":"Research progress of extracellular vesicles in type 2 diabetes and its complications","volume":"39","author":"Zhang","year":"2022","journal-title":"Diabet. 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