Beneficial effect of the insulin sensitizer (HSP inducer) BGP-15 on olanzapine-induced metabolic disorders.
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.
Literáti-Nagy
B
B
DRC (Drug Research Center) Ltd., 8230 Balatonfüred, Ady Endre u. 12, Hungary.
Péterfai
E
E
Kulcsár
E
E
Literáti-Nagy
Zs
Z
Buday
B
B
Tory
K
K
Mandl
J
J
Sümegi
B
B
Fleming
A
A
Roth
J
J
Korányi
L
L
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000633:toxicity*; D001569:Benzodiazepines / Q000633:toxicity*; D001786:Blood Glucose; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced*; D008875:Middle Aged; D000077152:Olanzapine; D010091:Oximes / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D013997:Time Factors
D014150:Antipsychotic Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010091:Oximes; D010880:Piperidines; D001569:Benzodiazepines; D000077152:Olanzapine; C405586:BGP 15