{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:16:13Z","timestamp":1778271373060,"version":"3.51.4"},"reference-count":244,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objective: In recent years, epidemiological and clinical evidence has suggested an association between the use of second-generation antipsychotics (SGAs) and hyperglycemic complications: notably, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). However, the role of first-generation antipsychotics (FGAs) remains less well understood. To conduct a systematic review of evidence established in case reports (CRs) on adverse drug reactions, specifically DKA and HHS, associated with the use of both FGAs and SGAs in order to identify patterns that may inform clinical awareness and future research. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using index phrases and keywords up until 17 October 2025. Eligible CRs discussed exposure to at least one US FDA-approved antipsychotic drug (APD) and assessed either DKA or HHS. Results: A total of 151 CRs were included in the systematic review (DKA, n = 121; HHS, n = 28; both conditions, n = 2). Patients aged 30 to 39 years accounted for the highest number of emergencies (n = 49, 32.5%), which occurred mostly in males (n = 108, 71.5%). The most common mental health diagnosis was schizophrenia (n = 77, 51%), followed by bipolar disorder (n = 26, 17.2%). Olanzapine was associated with the highest number of DKA cases (n = 53, 43.1%), followed by clozapine (n = 24, 19.5%). The average blood glucose at presentation was 842.8 mg\/dL for DKA patients and 1252.8 mg\/dL for HHS patients. The average hemoglobin A1c levels (HbA1c) were 11.5% and 12%, respectively, for these two conditions. Of the 12 reported fatalities, treatment with olanzapine was noted in four DKA cases and in one HHS case. Conclusions: This analysis provides additional evidence of an association between the use of atypical APDs and DKA or HHS. Clinicians should continue to monitor metabolic risk factors for these conditions, as well as educating patients about the prevention of acute diabetic complications.<\/jats:p>","DOI":"10.3390\/jcm15083107","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antipsychotic Drugs and the Risk of Diabetic Complications: A Systematic Review of Clinical Evidence"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-1425","authenticated-orcid":false,"given":"Nisrine","family":"Haddad","sequence":"first","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0291-0270","authenticated-orcid":false,"given":"Nawal","family":"Farhat","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"School of Mathematics and Statistics, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Gravel","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Mathematics and Statistics, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Data Literacy Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Momoli","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Risk Sciences International, Ottawa, ON K1Z 7T1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald R.","family":"Mattison","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Risk Sciences International, Ottawa, ON K1Z 7T1, Canada"},{"name":"Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannette","family":"Goguen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada"},{"name":"Division of Endocrinology, St. Michael\u2019s Hospital, Toronto, ON M5C 2T2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Krewski","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"School of Mathematics and Statistics, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Risk Sciences International, Ottawa, ON K1Z 7T1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mucci, F., Arone, A., Gurrieri, R., Weiss, F., Russomanno, G., and Marazziti, D. 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