Paliperidone-induced diabetes mellitus presenting with hyperosmolar hyperglycemic state: a case report

BACKGROUND: Second-generation antipsychotics (SGA) have been associated with adverse metabolic effects, including the development of diabetes mellitus (DM) and, in rare cases, life-threatening hyperglycemic emergencies such as diabetic ketoacidosis and hyperosmolar hyperglycemic state (HHS). Paliperidone, a more recently developed SGA, is generally considered to have a more favourable metabolic profile compared with older SGAs. OBJECTIVE: We report new-onset diabetes mellitus presenting as HHS, with paliperidone as a major precipitating factor besides an underlying infection. MATERIALS AND METHODS: We present a case detailing the patient's presenting symptoms, clinical findings, laboratory investigations and clinical course. RESULTS: We present a case of de novo diabetes mellitus presenting with HHS, with clinical suspicion that paliperidone acted as a major precipitating factor, in addition to transient infection-related insulin resistance. After adequate antibiotic treatment and discontinuation of paliperidone, the patient's insulin requirements declined rapidly, allowing discharge on metformin monotherapy. To our knowledge, this is the first case of HHS linked to paliperidone usage, although a limited number of case reports have described diabetic ketoacidosis in patients treated with paliperidone. Conclusion: This case highlights the need for vigilant metabolic monitoring following the initiation of SGAs, even those considered more favourable metabolically.

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Journal
Acta Clinica Belgica
Published
2026-08-28
DOI
https://doi.org/10.1080/17843286.2026.2719654
Primary Topic
Schizophrenia research and treatment
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article
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article

Paliperidone-induced diabetes mellitus presenting with hyperosmolar hyperglycemic state: a case report

Aurelie Vanthuyne, Lise Haems, Michiel Reunes, Marijn Speeckaert
Acta Clinica Belgica
Schizophrenia research and treatment
article

Paliperidone-induced diabetes mellitus presenting with hyperosmolar hyperglycemic state: a case report

Aurelie Vanthuyne, Lise Haems, Michiel Reunes, Marijn Speeckaert
article en

Abstract

BACKGROUND: Second-generation antipsychotics (SGA) have been associated with adverse metabolic effects, including the development of diabetes mellitus (DM) and, in rare cases, life-threatening hyperglycemic emergencies such as diabetic ketoacidosis and hyperosmolar hyperglycemic state (HHS). Paliperidone, a more recently developed SGA, is generally considered to have a more favourable metabolic profile compared with older SGAs. OBJECTIVE: We report new-onset diabetes mellitus presenting as HHS, with paliperidone as a major precipitating factor besides an underlying infection. MATERIALS AND METHODS: We present a case detailing the patient's presenting symptoms, clinical findings, laboratory investigations and clinical course. RESULTS: We present a case of de novo diabetes mellitus presenting with HHS, with clinical suspicion that paliperidone acted as a major precipitating factor, in addition to transient infection-related insulin resistance. After adequate antibiotic treatment and discontinuation of paliperidone, the patient's insulin requirements declined rapidly, allowing discharge on metformin monotherapy. To our knowledge, this is the first case of HHS linked to paliperidone usage, although a limited number of case reports have described diabetic ketoacidosis in patients treated with paliperidone. Conclusion: This case highlights the need for vigilant metabolic monitoring following the initiation of SGAs, even those considered more favourable metabolically.

Acta Clinica Belgica
Ghent University Hospital (BE), Research Foundation - Flanders (BE), Agenzia Sanitaria Regionale Abruzzo (IT)
Openalex Percentile: Top 9%
Schizophrenia research and treatment
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Paliperidone-induced diabetes mellitus presenting with hyperosmolar hyperglycemic state: a case report — Aurelie Vanthuyne, Lise Haems, et al. · Acta Clinica Belgica (2026) | TGRS Research Map | TGRS