Risk of diabetes mellitus associated with atypical antipsychotic use among Medicaid patients with bipolar disorder: a nested case-control study

Pharmacotherapy. 2007 Jan;27(1):27-35. doi: 10.1592/phco.27.1.27.


Study objective: To quantify the risk of diabetes mellitus associated with atypical antipsychotics compared with conventional antipsychotics in managed care Medicaid patients with bipolar disorder.

Design: Retrospective nested case-control study.

Data source: Integrated seven-state Medicaid managed care claims database from January 1, 1998-December 31, 2002.

Patients: Two hundred eighty-three patients with diabetes (cases) and 1134 controls matched by age, sex, and the index date on which bipolar disorder was diagnosed.

Measurements and main results: Cases were defined as those having an International Classification of Diseases, Ninth Revision diagnosis of diabetes or those receiving treatment with antidiabetic drugs. Both case and control patients had at least a 3-month exposure to either conventional or atypical antipsychotic agents or three filled prescriptions related to treatment for bipolar disorder. Of the 283 cases, 139 (49%) received atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, and clozapine) and 133 (47%) were prescribed conventional antipsychotics. To compare the risk for new-onset diabetes associated with atypical versus conventional antipsychotics, we conducted a Cox proportional hazard regression, in which we controlled for age; sex; duration of bipolar disorder follow-up; use of lithium, anticonvulsants, antidepressants, and other drugs; and psychiatric and medical comorbidities. Compared with patients receiving conventional antipsychotics, the risk of diabetes was greatest among patients taking risperidone (hazard ratio [HR] 3.8, 95% confidence interval [CI] 2.7-5.3), olanzapine (3.7, 95% CI 2.5-5.3), and quetiapine (2.5, 95% CI 1.4-4.3). The risk for developing diabetes was also associated with weight gain (HR 2.5, 95% CI 1.9-3.4), hypertension (HR 1.6, 95% CI 1.2-2.2), and substance abuse (HR 1.5, 95% CI 1.0-2.2).

Conclusion: Olanzapine, risperidone, and quetiapine are all associated with development or exacerbation of diabetes mellitus in patients with bipolar disorder. When prescribing therapy for this patient population, metabolic complications such as diabetes, weight gain, and hypertension need to be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Case-Control Studies
  • Child
  • Diabetes Mellitus / epidemiology*
  • Diabetes Mellitus / etiology
  • Female
  • Humans
  • Male
  • Medicaid
  • Middle Aged
  • Risk Factors


  • Antipsychotic Agents