Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study

Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.


Objective: The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors, including weight gain, lipid abnormalities, age, clozapine dose, and treatment with valproate.

Method: Data on age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation were collected from medical records of 82 outpatients with schizophrenia or schizoaffective disorder. Clozapine dose, data on use of valproate, and laboratory test results were recorded at 6-month intervals.

Results: The mean age at the time of clozapine initiation of the 82 patients was 36.4 years; 26.8% of the patients were women, and 91.5% were Caucasian. The mean baseline weight was 175.5 lb, and the mean body mass index was 26.9 kg/m(2). Thirty patients (36.6%) were diagnosed with diabetes during the 5-year follow-up. Weight gain, use of valproate, and total daily dose of clozapine were not significant risk factors for developing diabetes mellitus. Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine. There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level.

Conclusions: The results support the hypotheses that patients treated with clozapine experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Age Factors
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Body Mass Index
  • Body Weight / drug effects*
  • Cholesterol / blood
  • Clozapine / adverse effects*
  • Clozapine / therapeutic use
  • Diabetes Mellitus / chemically induced*
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Dose-Response Relationship, Drug
  • Family
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hypercholesterolemia / chemically induced*
  • Hypercholesterolemia / epidemiology
  • Hypertriglyceridemia / chemically induced
  • Hypertriglyceridemia / epidemiology
  • Hypertriglyceridemia / genetics
  • Incidence
  • Male
  • Obesity / chemically induced
  • Obesity / epidemiology
  • Psychotic Disorders / drug therapy
  • Risk Factors
  • Schizophrenia / drug therapy
  • Triglycerides / blood
  • Valproic Acid / therapeutic use


  • Antipsychotic Agents
  • Triglycerides
  • Valproic Acid
  • Cholesterol
  • Clozapine