Unraveling the Mechanisms Underlying Olanzapine-Induced Insulin Resistance

  1. Victor Alan Gault2
  1. 1School of Pharmacy and Pharmaceutical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, U.K.
  2. 2School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, U.K.
  1. Corresponding author: Victor Alan Gault, va.gault{at}ulster.ac.uk.

Atypical antipsychotics (AAPs) are widely prescribed agents for treatment of schizophrenia and other related psychiatric disorders. Although AAPs were a major development in psychopharmacology, so-called second-generation agents such as olanzapine have exhibited unexpected and unfavorable metabolic side effects. These side effects include weight gain, glucose intolerance, and insulin resistance, all of which increase the likelihood of developing diabetes and cardiovascular disease (1). Nonetheless, how these adverse metabolic effects arise following AAP treatment remains unclear. A key question is whether AAP-associated metabolic impairments are because of the psychiatric illness itself or if they are merely secondary to weight gain.

In this issue, Teff et al. (2) examine the direct effects of second-generation AAPs on insulin resistance and postprandial gut hormone profiles following a mixed meal. The antipsychotic drugs used in these experiments—olanzapine and aripiprazole—were administered to healthy volunteers for 9 consecutive days to exclude potential confounding issues associated with psychiatric disease …

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