title: The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance.
abstract: Therapeutic use of atypical antipsychotic agents is often associated with weight gain and impaired glucose tolerance. The once-daily human GLP-1 analog liraglutide improves glycemic control and reduces body weight. We have investigated the ability of liraglutide to improve olanzapine-induced metabolic effects in female rats. Female Sprague-Dawley rats were implanted with subcutaneous osmotic mini pumps for delivery of olanzapine (1.75 mg/24 h) or vehicle for 28 days (n=20). After 14 days, ten animals from each group were given liraglutide (0.2 mg/kg) or vehicle twice daily for the remainder of the study. Compared to vehicle treated animals, olanzapine infusion for 4 weeks significantly increased end point cumulated food intake (667.3+/-7.0 versus 593.2+/-13.2g, p<0.01), body weight (306.6+/-4.2 versus 276.4+/-3.6 g, p<0.001), subcutaneous inguinal fat (3.4+/-0.3 versus 1.9+/-0.1 g, p<0.001), mesenteric fat (3.1+/-0.2 versus 1.7+/-0.2g, p<0.001), retroperitoneal fat (6.2+/-0.6 versus 2.8+/-0.3 g, p<0.001), and impaired glucose tolerance, measured as total area under the glucose curve during an oral glucose tolerance test (1906+/-66 versus 1770+/-28 mMxmin, p<0.05). These olanzapine-induced elevations were significantly reduced by liraglutide (cumulated food intake: 601.8+/-20.4 g, p<0.01; body weight: 280.2+/-5.6 g, p<0.001; subcutaneous inguinal fat: 2.4+/-0.2 g, p<0.001; mesenteric fat: 1.8+/-0.1 g, p<0.001; retroperitoneal fat: 3.5+/-0.4 g, p<0.001; AUC: 1764+/-32 mMxmin, p<0.05). In conclusion, subcutaneous olanzapine infusion in female rats leads to weight gain and metabolic changes of which several are reversed following liraglutide treatment. It may therefore be relevant to study these effects of liraglutide in patients treated with atypically antipsychotics.
authors.affiliation: Rheoscience A/S, Glerupvej 2, DK-2610 Roedovre, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lykkegaard
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Larsen
authors.forename: Niels
authors.initials: N
authors.lastname: Vrang
authors.forename: Camilla
authors.initials: C
authors.lastname: Bock
authors.forename: Troels
authors.initials: T
authors.lastname: Bock
authors.forename: Lotte Bjerre
authors.initials: LB
authors.lastname: Knudsen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000517:prevention & control; D005951:Glucose Tolerance Test; D050152:Intra-Abdominal Fat / Q000187:drug effects; D000069450:Liraglutide; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077152:Olanzapine