Atypical Antipsychotics tied to Risk of Acute Diabetic Complications, confirms study
Researchers have found in a new study the findings of which reinforce the association between atypical antipsychotic use and an increased risk of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The study highlights the need for regular monitoring of metabolic risk factors and emphasizes the importance of patient education to help prevent these serious acute complications.
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.
Reference:
Haddad N, Farhat N, Gravel CA, Chen Y, Momoli F, Mattison DR, Goguen J, Krewski D. Antipsychotic Drugs and the Risk of Diabetic Complications: A Systematic Review of Clinical Evidence. Journal of Clinical Medicine. 2026; 15(8):3107. https://doi.org/10.3390/jcm15083107
