Beneficial effect of the insulin sensitizer (HSP inducer) BGP-15 on olanzapine-induced metabolic disorders

• Published in: Brain research bulletin Vol. 83; no. 6; pp. 340 - 344
• Main Authors: Literáti-Nagy, B, Péterfai, É, Kulcsár, E, Literáti-Nagy, Zs, Buday, B, Tory, K, Mandl, J, Sümegi, B, Fleming, A, Roth, J, Korányi, L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.11.2010
• Subjects: Adult; Age; Analysis of Variance; Antipsychotic Agents - toxicity; Benzodiazepines - toxicity; BGP-15; Blood Glucose; Double-Blind Method; Fasting; Female; Glucose Clamp Technique - methods; Glucose Tolerance Test; Glucose utilization; Humans; Hyperinsulinemic-euglycemic clamp; Hypoglycemic Agents - therapeutic use; Insulin resistance; Male; Metabolic Diseases - chemically induced; Middle Aged; Neurology; Olanzapine; Oximes - therapeutic use; Piperidines - therapeutic use; Time Factors; Olanzapine; HSP; Hyperinsulinemic-euglycemic clamp; intravenous glucose tolerance tests; JNK; least-squares mean; AAPD; heat shock protein; LSMean; area under the curve; BGP-15; AUC; atypical antipsychotic drug; DEXA; IVGTT; dual-energy X-ray absorption; Insulin resistance; c-jun n-terminal kinase; Glucose utilization
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2010.09.005

Abstract 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 400 mg of BGP-15 or placebo and 5 mg of olanzapine for 3 days followed by 10 mg 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.