Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses

J Clin Psychiatry. 2000 Oct;61(10):742-9. doi: 10.4088/jcp.v61n1006.


Background: The aim of this study was to investigate the influence of the antipsychotic agent olanzapine on glucose-insulin homeostasis to explain possible mechanisms behind olanzapine-associated weight gain.

Method: Fourteen patients on treatment with olanzapine (all meeting DSM-IV criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose, insulin, the growth hormone (GH)-dependent insulin-like growth factor I, and the insulin-dependent insulin-like growth factor binding protein-1 (IGFBP-1) were analyzed, as well as GH, leptin, and blood lipid levels and the serum concentrations of olanzapine and its metabolite N-desmethylolanzapine. In addition, body mass index (BMI) was calculated. Moreover, weight change during olanzapine treatment was determined.

Results: Twelve of the 14 patients reported weight gain between 1 and 10 kg during a median olanzapine treatment time of 5 months, whereas data were not available for the other 2 patients. Eight patients (57%) had BMI above the normal limit. Eleven patients were normoglycemic, and 3 showed increased blood glucose values. Most patients (10/14; 71%) had elevated insulin levels (i.e., above the normal limit). Accordingly, the median value of IGFBP-1 was significantly lower for the patients in comparison with healthy subjects. Moreover, 8 (57%) of 14 patients had hyperleptinemia, 62% (8/13) had hypertriglyceridemia, and 85% (11/13) hypercholesterolemia. Weight change correlated positively to blood glucose levels and inversely to the serum concentration level of N-desmethylolanzapine. Additionally, the levels of blood glucose, triglycerides, and cholesterol correlated inversely to the serum concentration of N-desmethylolanzapine.

Conclusion: Olanzapine treatment was associated with weight gain and elevated levels of insulin, leptin, and blood lipids as well as insulin resistance, with 3 patients diagnosed to have diabetes mellitus. Both increased insulin secretion and hyprleptinemia may be mechanisms behind olanzapine-induced weight gain. Moreover, it is suggested that the metabolite N-desmethylolanzapine, but not olanzapine, has a normalizing effect on the metabolic abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines
  • Blood Glucose / analysis
  • Body Weight
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Insulin / blood*
  • Leptin / blood*
  • Lipids / blood*
  • Male
  • Middle Aged
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / blood
  • Pirenzepine / therapeutic use*
  • Psychotic Disorders / blood*
  • Psychotic Disorders / drug therapy*
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy*
  • Triglycerides / blood


  • Antipsychotic Agents
  • Blood Glucose
  • Insulin
  • Leptin
  • Lipids
  • Triglycerides
  • Benzodiazepines
  • Pirenzepine
  • Olanzapine