Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach

Arch Gen Psychiatry. 2001 Dec;58(12):1172-6. doi: 10.1001/archpsyc.58.12.1172.


Background: Numerous case reports have linked clozapine to the development of diabetes mellitus and hyperlipidemia in patients with schizophrenia. However, investigators have been unable to clearly demonstrate this association when compared with a control group receiving conventional antipsychotics.

Methods: Medical and pharmacy claims from the Iowa Medicaid program were used to compare incidence rates for diabetes, hyperlipidemia, and hypertension in 552 patients receiving clozapine and 2461 patients receiving conventional antipsychotics (eg, haloperidol, chlorpromazine hydrochloride), with the use of a retrospective cohort design. Logistic regression was used to compare incidence rates adjusting for age, sex, and duration of available follow-up.

Results: No significant differences in overall incidence rates for diabetes, hyperlipidemia, or hypertension were observed in patients receiving clozapine vs conventional antipsychotics. However, among younger patients (aged 20-34 years), clozapine administration was associated with a significantly increased relative risk of diabetes (2.5 [95% confidence interval, 1.2-5.4]) and hyperlipidemia (2.4 [95% confidence interval, 1.1-5.2]), but not hypertension (0.9 [95% confidence interval, 0.4-2.0]).

Conclusions: These data suggest that clozapine may not be an independent cause of diabetes or hyperlipidemia, but instead acts as an effect modifier in susceptible populations by increasing weight or affecting insulin secretion and resistance. This finding requires confirmation in other settings and patient populations and with the other atypical antipsychotics (risperidone, olanzapine, and quetiapine fumarate). The potential long-term medical and economic implications of the early induction of diabetes and hyperlipidemia in patients with schizophrenia warrant further study.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Causality
  • Clozapine / adverse effects*
  • Clozapine / therapeutic use
  • Cohort Studies
  • Confidence Intervals
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperlipidemias / chemically induced*
  • Hyperlipidemias / diagnosis
  • Hyperlipidemias / epidemiology
  • Hypertension / chemically induced*
  • Hypertension / diagnosis
  • Hypertension / epidemiology
  • Incidence
  • Iowa
  • Male
  • Middle Aged
  • Product Surveillance, Postmarketing
  • Retrospective Studies
  • Risk
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology


  • Antipsychotic Agents
  • Clozapine