{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:21:30Z","timestamp":1791055290279,"version":"4.1.0"},"reference-count":191,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. Currently, SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. Thus, the substantial interest in SGLT-2 inhibitors (SGLT-2is) underlines the present review. It begins with an overview of carrier-mediated cellular glucose uptake, evidencing the insulin-independent transport system contribution to glucose homeostasis and the essential roles of Sodium-Glucose Cotransporters 1 and 2. Then, the pharmacological properties of SGLT-2is are detailed, leading to potential applications in treating T1DM patients with automated insulin delivery (AID) systems. Results from several studies demonstrated improvements in glycemic control, an increase in Time in Range (TIR), a decrease in glycemic variability, reduced daily insulin requirements without increasing hyperglycemic events, and benefits in weight management. However, these advantages are counterbalanced by increased risks, particularly concerning Diabetic Ketoacidosis (DKA). Several clinical trials reported a higher incidence of DKA when patients with T1DM received SGLT-2 inhibitors such as Sotagliflozin and Empagliflozin. On the other hand, patients with T1DM and a body mass index (BMI) of \u226527 kg\/m2 treated with Dapagliflozin showed similar reduction in hyperglycemia and body weight and insignificantly increased DKA incidence compared to the overall trial population. Additional multicenter and randomized studies are required to establish safer and more effective long-term strategies based on patient selection, education, and continuous ketone body monitoring for optimal integration of SGLT-2 inhibitors into T1DM therapeutic protocol.<\/jats:p>","DOI":"10.3390\/ijms25041972","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T07:50:12Z","timestamp":1707205812000},"page":"1972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems\u2014A Literature Review"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-8051","authenticated-orcid":false,"given":"Viviana","family":"Elian","sequence":"first","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 5-7 Ion Movila Street, 020475 Bucharest, Romania"},{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, \u201cN. C. Paulescu\u201d National Institute of Diabetes, Nutrition and Metabolic Diseases, 020475 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9696-5728","authenticated-orcid":false,"given":"Violeta","family":"Popovici","sequence":"additional","affiliation":[{"name":"\u201cCostin C. Kiri\u0163escu\u201d National Institute of Economic Research\u2014Center for Mountain Economics (INCE-CEMONT) of Romanian Academy, 725700 Vatra-Dornei, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Karampelas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gratiela Gradisteanu","family":"Pircalabioru","sequence":"additional","affiliation":[{"name":"eBio-Hub Research Centre, National University of Science and Technology Politehnica Bucharest, 061344 Bucharest, Romania"},{"name":"Research Institute, University of Bucharest, 061344 Bucharest, Romania"},{"name":"Academy of Romanian Scientists, 54 Splaiul Independentei, 050094 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Radulian","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 5-7 Ion Movila Street, 020475 Bucharest, Romania"},{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, \u201cN. C. Paulescu\u201d National Institute of Diabetes, Nutrition and Metabolic Diseases, 020475 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina","family":"Musat","sequence":"additional","affiliation":[{"name":"eBio-Hub Research Centre, National University of Science and Technology Politehnica Bucharest, 061344 Bucharest, Romania"},{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 030167 Bucharest, Romania"},{"name":"Department of Endocrinology IV, \u201cC. I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1038\/s41467-023-38720-1","article-title":"Structures of Human SGLT in the Occluded State Reveal Conformational Changes during Sugar Transport","volume":"14","author":"Cui","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C6","DOI":"10.1152\/ajpcell.00444.2010","article-title":"Molecular Determinants of Renal Glucose Reabsorption. Focus on \u201cGlucose Transport by Human Renal Na+\/d-Glucose Cotransporters SGLT1 and SGLT2\u201d","volume":"300","author":"Vallon","year":"2011","journal-title":"Am. J. Physiol. 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