Beneficial effect of the insulin sensitizer (HSP inducer) BGP-15 on olanzapine-induced metabolic disorders.
Author(s): Literati-Nagy B, Peterfai E, Kulcsar E, Literati-Nagy Z, Buday B, Tory K, Mandl J, Sumegi B, Fleming A, Roth J, Koranyi L
Affiliation(s): DRC (Drug Research Center) Ltd., 8230 Balatonfured, Ady Endre u. 12, Hungary.
Publication date & source: 2010-11-20, Brain Res Bull., 83(6):340-4. Epub 2010 Sep 16.
Publication type: Clinical Trial; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Olanzapine is a widely used atypical antipsychotic, with well known metabolic side effects such as weight gain, insulin resistance and blood glucose abnormalities. It has been previously shown in a phase II clinical trial that BGP-15, an amidoxim derivative has insulin-sensitizing effects. The aim of this study was to investigate the efficacy of BGP-15 for the treatment of olanzapine-induced metabolic side effects, in healthy volunteers. Thirty-seven (37) subjects (ages 18-55 years) with normal glucose metabolism were randomly assigned to 17 days of once-daily treatment with 400mg of BGP-15 or placebo and 5mg of olanzapine for 3 days followed by 10mg for 14 days. Total body and muscle tissue glucose utilization was determined by hyperinsulinemic-euglycemic clamp technique. As expected the 17-day olanzapine treatment provoked insulin resistance and body weight gain (p<0.05) in both groups. Administration of BGP-15 significantly reduced olanzapine-induced insulin resistance. The protective effect of BGP-15 on insulin stimulated glucose utilization had the highest magnitude in the values calculated for the muscle tissue (p=0.002). In healthy individuals BGP-15 was safe and well tolerated during the whole study period. It is suggested that BGP-15 can be a successful insulin sensitizer agent to prevent side effects of olanzapine treatment. 2010 Elsevier Inc. All rights reserved.