二甲双胍联合行为干预治疗抗精神病药所致体质量增加及糖代谢紊乱的研究

目的验证二甲双胍与行为干预单一或联合治疗抗精神病药所致的体质量增加及糖代谢紊乱的疗效。方法将抗精神病药所致体质量增加≥10％的128例精神分裂症患者随机分为四组：二甲双胍（750mg／d）联合行为于预组（以下简称A组，32例）；二甲双胍（750mg／d）组（以下简称B组，32例）；行为干预联合安慰剂组（以下简称C组，32例）；安慰剂对照组（以下简称D组，32例）；治疗观察期均为12周。四组患者于治疗前及治疗后第4，8，12周末测定空腹血糖、胰岛素、身高、体质量、腰围，计算体质量指数（BMI）及胰岛素抵抗指数（IRI）并进行比较。结果（1）A、B、C组患者治疗后的体质量、BMI、空腹血糖、空腹胰岛素及IRI均明显低于治疗前（P〈0．05）；D组患者的体质量、BMI、腰围、空腹胰岛素、IRI治疗后均明显高于治疗前（P〈0，05）。（2）治疗4周末，A组与B组体质量、BMI的下降程度相同，但均明显高于C组。治疗12周末，体质量、BMI的下降程度以A组最高，其次为B组和C组。治疗后各时点，A组与B组的空腹胰岛素、IRI的下降程度相同，均明显高于C组。结论二甲双胍与行为干预单一或联合治疗均能有效减轻抗精神病药所致的体质量增加及胰岛素抵抗，二甲双胍联合行为干预的疗效最好。单用二甲双胍与二甲双胍联合行为干预治疗缓解抗精神病药引起的胰岛素抵抗的疗效相同。     

降糖药联合行为干预治疗非典型抗精神病药所致代谢综合征的研究

目的 验证降糖药二甲双胍与行为干预联合治疗非典型抗精神病药所致代谢综合征的疗效.方法 将抗精神病药所致体质量增加≥10%的128例精神分裂症患者随机分为四组:二甲双胍(750 mg/d)联合行为干预组(以下简称A组,32例);二甲双胍(750 mg/d)组(以下简称B组,32例);行为干预联合安慰剂组(以下简称C组,32例);安慰剂对照组(以下简称D组,32例);治疗观察期均为12周.结果 A、B、C组患者治疗后的体质量、BMI、空腹血糖、空腹胰岛素及IRI均明显低于治疗前(P(0.05);D组患者的体质量、BMI、腰围、空腹胰岛素、IRI治疗后均明显高于治疗前(P<0.05).结论 二甲双胍与行为干预单一或联合治疗均能有效减轻非典型抗精神病药所致的代谢综合征,二甲双胍联合行为干预的疗效最好.     

奥氮平与阿立哌唑对首发精神分裂症糖脂代谢影响的对照研究

目的 研究阿立哌唑、奥氮平对首发精神分裂症患者血糖及血脂代谢的影响.方法 随机将61例首发精神分裂症患者分为奥氮平组和阿立哌唑组,比较治疗前及治疗后第6周末两组患者身高、体质量、血糖（FBG）、胰岛素（INS）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、甘油三酯（TG）、总胆固醇（TC）变化.结果 治疗后第6周末奥氮平组FBG、INS、IRI、LDL、TG、TC、体质量及BMI均较治疗前明显升高（P＜0.05,P＜0.01）,治疗后第6周末奥氮平组上述指标较阿立哌唑组高（P＜0.05）.结论 与奥氮平相比,阿立哌唑对首发精神分裂症患者FBG及血脂代谢影响较轻.     

低能量膳食对奥氮平所致体质量增加的男性精神分裂症患者糖脂代谢的影响

目的:探讨低能量膳食对奥氮平所致体质量增加的男性精神分裂症患者糖脂代谢的影响。方法:选择2018年4月至2019年4月124例奥氮平所致体重增加的精神分裂症患者为研究对象,按照随机数字法分为A组(奥氮平片20 mg/d)、B组(奥氮平片20 mg/d联合二甲双胍片750 mg/d)和C组(奥氮平片20 mg/d联合低能量膳食)。比较3组患者治疗前和治疗3个月后体质量指数和糖脂代谢的变化。结果:治疗3个月后,A组体质量指数、空腹血糖、餐后2 h血糖、总胆固醇、三酰甘油、低密度脂蛋白胆固醇均高于B组和C组,高密度脂蛋白胆固醇低于B组和C组(P均0.05)。B组低密度脂蛋白胆固醇高于C组(P0.05),B组和C组在体质量指数、空腹血糖和餐后2 h血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇方面差异无统计学意义(P均0.05)。结论:低能量膳食控制奥氮平所致体重增加的男性精神分裂症患者糖脂代谢水平的疗效与二甲双胍相当,提示膳食干预可作为该群体糖脂代谢异常的非药物性干预方案。     

阿立哌唑治疗奥氮平所致精神分裂症患者体质量增加的随机双盲对照研究

目的:探讨阿立哌唑干预奥氮平所致体质量增加的有效性及安全性。方法:将服用单一奥氮平治疗所致体质量增加≥7%的入组对象72例随机分为A组(加服阿立哌唑10 mg组,36例)及B安慰剂组(36例),入组时、治疗4周及8周分别测定体质量、体质量指数(BMI)、空腹血糖(FG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL),并用阳性和阴性症状量表(PANSS)评定精神症状。结果:两组治疗前体质量、BMI、FG、TC、TG、LDL、HDL,差异无统计学意义(P0.05)。与治疗前比较,治疗8周,A组体质量、BMI、FG均明显下降(P0.05或P0.01),而HDL有明显增高(P0.05);B组体质量、BMI、FG均明显增高(P0.05或P0.01)。治疗4周体质量、BMI的变化值、治疗第8周体质量、BMI、FG、HDL的变化值,两组均差异有统计学意义(P0.05或P0.01)。结论:阿立哌唑能有效减轻奥氮平所致体质量增加和糖脂代谢紊乱。     

奥氮平合并不同剂量二甲双胍对精神分裂症患者体质量和糖脂代谢的影响

目的:探讨二甲双胍早期干预对精神分裂症患者体质量和糖脂代谢的有效性和安全性。方法:150例首发精神分裂症患者分为治疗组(奥氮平联合二甲双胍)和对照组30例(奥氮平单药),治疗组根据联合二甲双胍不同剂量(即奥氮平10～20 mg/d+二甲双胍250 mg/d、500 mg/d、750 mg/d)分为治疗1组(30例)、治疗2组(30例)及治疗3组(28例)。分别于治疗前和治疗4、8及12周测定体质量指数(BMI)及空腹血糖(FBG)、糖化血红蛋白(HbA 1c)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL);采用阳性和阴性症状量表(PANSS)治疗前后评定疗效,并记录不良事件评定安全性。结果:治疗12周,各组体质量及BMI均较治疗前显著增加,治疗3组与对照组比较差异有统计学意义(χ2=10.138,t=2.905;P0.01);各组TC、TG、LDL、对照组及治疗1组FBG、HbA 1c较治疗前增加(P均0.05)、HDL较治疗前降低(P0.05);各组间比较,治疗2组和治疗3组TC、TG、HDL、LDL与对照组比较差异有统计学意义(P均0.05);治疗3组胃肠道不适症状较多。结论:早期合并二甲双胍(500 mg/d)干预奥氮平所致的体质量增加和糖脂代谢紊乱的效果有限。     

氨磺必利替换奥氮平治疗对伴有代谢综合征精神分裂症患者的影响

目的:观察氨磺必利替换奥氮平治疗对伴有代谢综合征精神分裂症患者的影响。方法:92例奥氮平治疗伴代谢综合征的精神分裂症患者随机分为氨磺必利组(治疗组)及奥氮平组(对照组)各46例。治疗组在2周内将奥氮平换为氨磺必利,对照组维持奥氮平治疗,观察12周。入组时及第6、12周末测量腰围、血压、体质量指数(BMI)及空腹血糖(FBS)、高密度脂蛋白(HDL)、三酰甘油(TG)水平。应用阳性和阴性症状评定量表(PANSS)和治疗中出现的症状量表(TESS)进行疗效和安全性评定。结果:治疗12周末,治疗组腰围、收缩压、BMI、TG、FBS均显著低于对照组(P0.05或P0.01),两组PANSS评分差异无统计学意义(P0.05),而TESS评分治疗组低于对照组(P0.05)。结论:氨磺必利替换奥氮平治疗对精神分裂症患者体质量增加及代谢综合征有显著改善作用。     

二甲双胍对奥氮平治疗后体质量显著增加的男性精神分裂症患者血清睾酮水平的影响

目的:探讨二甲双胍对奥氮平治疗后体质量显著增加的男性精神分裂症患者血清睾酮水平的影响。方法:奥氮平治疗后体质量显著增加(≥7%)的男性精神分裂症患者随机分为研究组(n=28)与对照组(n=29),维持原奥氮平治疗方案不变。两组均给予生活方式干预,研究组在生活方式干预基础上加用二甲双胍(1 500 mg/d)治疗,为期3个月。于治疗前、治疗后测定睾酮水平、体质量指数(BMI)。结果:研究组治疗后睾酮水平(t=2.76,P0.05)、BMI(t=3.62,P0.01)较治疗前下降,对照组治疗前后睾酮水平、BMI差异无统计学意义(P均0.05);研究组治疗后睾酮水平(t=-2.34,P0.05)、BMI(t=-2.09,P0.05)均低于对照组。研究组治疗前后睾酮水平的变化值与BMI的变化值无显著相关性(r=0.078,P0.05)。结论:二甲双胍可降低奥氮平所致体质量增加的男性精神分裂症患者的睾酮水平,这一作用独立于二甲双胍的降重作用。     

奥氮平联用氟西汀治疗精神分裂症阴性症状的对照研究

目的 探讨奥氮平合并氟西汀治疗精神分裂症阴性症状的疗效和安全性.方法 将59例以阴性症状为主的精神分裂症患者随机分为研究组(奥氮平合用氟西汀治疗,30例)和对照组(单用奥氮平治疗,29例),于治疗前和治疗后第2、4、8、12周末使用阳性和阴性综合征量表(PANSS)和阴性症状量表(SANS)评定两组的疗效,药物治疗中需处理的不良反应症状量表(TESS)评定两组的不良反应.结果 治疗后第2周末研究组PANSS总分、阴性因子分较治疗前降低,差异有统计学意义(P＜0.05),治疗后第4周末研究组PANSS总分、阴性因子分及SANS总分、情感平淡因子分明显低于对照组,差异有统计学意义(P＜0.05,P＜0.01).两组TESS评分体质量改变差异有统计学意义(P＜0.05),余无明显差异.结论 奥氮平合并氟西汀能显著改善精神分裂症患者的阴性症状,且安全性好.     

托吡酯与二甲双胍治疗抗精神病药致肥胖的疗效的对照研究

目的:探讨托吡酯与二甲双胍治疗抗精神病药致肥胖的作用及安全性。方法:随机将62例抗精神病药致肥胖、且病情稳定的精神分裂症患者分为托吡酯组及二甲双胍组;在原抗精神病药种类、剂量治疗的基础上分别给予托吡酯及二甲双胍。分别于干预前、干预后进行阳性和阴性症状量表(PANSS)评估,测量体质量、体质量指数(BMI)、腰臀比(WHR),并进行安全性评价。结果:(1)与基线比较,托吡酯组在第4、8、12周时体质量、BMI、WHR,第12周时PANSS总分及一般病理分差异有统计学意义(P均0.01);二甲双胍组在第4、8、12周时WHR,在第8、12周时体质量、BMI,第12周时PANSS总分差异均有统计学意义(P0.05或P0.01)。(2)干预后,托吡酯组各时间点体质量变化率,第4、8周WHR明显高于二甲双胍组(P0.05或P0.01),PANSS总分、阴性症状分、一般病理分明显低于二甲双胍组(P均0.01);体质量下降7%的比例两组比较差异无统计学意义。(3)干预38周后两组体质量、BMI与基线相比差异有统计学意义(P均0.05)。结论:托吡酯、二甲双胍辅助治疗降低抗精神病药致肥胖患者的体质量的近、远期作用显著,安全性好;且托吡酯的作用更优,改善患者阴性症状。     

Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: a double-blind, placebo-controlled study

OBJECTIVE: The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain. METHOD: Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15 mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This investigation was conducted in a double-blind fashion. Planned assessments included body weight, body mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12-week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). RESULTS: Of the 40 patients who were randomly assigned, 37 (92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no between-group differences. Metformin was tolerated well by all patients. CONCLUSIONS: Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients. Patients displayed good adherence to this type of preventive intervention.     

Metformin for prevention of weight gain and insulin resistance with olanzapine: a double-blind placebo-controlled trial.

OBJECTIVE: To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine. METHOD: Forty patients taking olanzapine (10 mg daily) were randomly allocated to a metformin (n = 20; 850 to 1700 mg daily) or placebo (n = 20) group in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at Weeks 7 and 14 of treatment. RESULTS: At Week 14, BWG (kg) was similar in the metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no differences between the changes in BMI, WC, glucose, insulin, insulin resistance index (HOMA-IR), and plasma lipid levels observed in the treatment group and the placebo group; however, glucose levels decreased significantly after metformin administration (P = 0.02). The HOMA-IR decreased significantly in both groups, but 3 subjects from the placebo group developed fasting glucose levels greater than 5 mmol/L. After taking metformin, triglyceride levels increased, but the cholesterol profile improved significantly. CONCLUSIONS: Metformin did not prevent olanzapine-induced BWG. While some lipid parameters worsened during placebo, the HOMA-IR improved in both the placebo and the metformin groups. Carbohydrate metabolism impairment was not systematically observed during short-term olanzapine administration.     

Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial

BACKGROUND: Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables. METHODS: Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment. RESULTS: The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels. CONCLUSIONS: Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.     

Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind,placebo-controlled study

OBJECTIVE: Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants, the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain. METHOD: Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study. In addition to 6 weeks of treatment with olanzapine, 10 mg/day, patients were randomly allocated in a double-blind design to receive either reboxetine, 4 mg/day, (N=13) or placebo (N=13). RESULTS: Ten patients in each group completed the 6-week trial. Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1). Significantly fewer patients in the olanzapine/reboxetine group (N=2 of 10) than in the olanzapine/placebo group (N=7 of 10) gained at least 7% of their initial weight, the cutoff for clinically significant weight gain. The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients. A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group (mean difference=-3.1, SD=1.25). CONCLUSIONS: The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents.     

二甲双胍合并行为干预疗法对氯氮平治疗精神分裂症患者体重、血糖、血脂的影响

目的探讨二甲双胍合并行为干预疗法对氯氮平治疗精神分裂症患者体重、血糖、血脂的影响。方法将60例开始单独服用氯氮平治疗的精神分裂症患者随机分为两组,研究组采用氯氮平（250～400mg/d）联合二甲双胍（750mg/d）及实施行为干预治疗,对照组则单用氯氮平（250～400mg/d）,未实施任何干预措施,治疗12周。两组患者分别于入组时和治疗后第4、8及12周末测定空腹血糖（FBG）、血脂（TC、TG、HDL、LDL）、身高、体重、腰围,计算体重指数（BMI）以及治疗12周末体重增加大于7%的人数比率。用阴性与阳性症状量表（PANSS）于治疗前和治疗12周末评定疗效。结果治疗12周末,研究组与对照组体重较治疗前分别增加为（2.03±1.26）kg、（4.98±3.09）kg;BMI较治疗前分别增加为（0.54±0.62）kg/m2、（2.03±1.02）kg/m2,体重、BMI的升高程度对照组高于研究组（P〈0.05）,体重增加大于7%的患者研究组为6例（20%）、对照组为16例（53%）,对照组明显高于研究组（P〈0.05）。两组患者治疗后空腹血糖、血脂各项的升高程度对照组明显高于研究组（P〈0.05）。结论二甲双胍合并行为干预疗法能有效减轻氯氮平治疗精神分裂症患者所致的体重增加及血糖、血脂升高。     

A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents

OBJECTIVE: Second-generation, or atypical, antipsychotics effectively treat psychiatric illness in children and adolescents. However, weight gain and abnormalities in insulin sensitivity, including diabetes, complicate this therapy. METHOD: A 16-week double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of metformin in managing weight gain in 39 subjects, ages 10-17, whose weight had increased by more than 10% during less than 1 year of olanzapine, risperidone, or quetiapine therapy. Body weight, body mass index (kilograms per square meter of height), and waist circumference were measured regularly, as were fasting insulin and glucose levels. RESULTS: Weight was stabilized in subjects receiving metformin, while those receiving placebo continued to gain weight (0.31 kg/week). Because the study was conducted with growing children, metformin treatment resulted in reduction in z scores for both weight and body mass index. The homeostasis model assessment, a surrogate indicator of insulin sensitivity, decreased in treated subjects. Overt diabetes was diagnosed in two subjects before treatment (elevated baseline fasting glucose and insulin values) and in two placebo-treated subjects (one at week 12 and the other after study completion). One subject taking placebo developed impaired fasting glucose. Placebo treatment was associated with the need to perform oral glucose tolerance testing upon study completion, by which three additional subjects were identified with impaired glucose tolerance. No serious adverse events resulted from metformin treatment. CONCLUSIONS: Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypicals.     

Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind,placebo-controlled study of fluoxetine addition

OBJECTIVE: Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor, the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine. METHOD: First-episode hospitalized schizophrenia patients (N=30) were randomly assigned in an 8-week double-blind study of olanzapine, 10 mg/day, coadministered with either fluoxetine, 20 mg/day (N=15), or placebo (N=15). RESULTS: The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo. The two groups demonstrated similar and substantial gradual weight gains. CONCLUSIONS: These results suggest that fluoxetine coadministration is clinically ineffective and cannot attenuate olanzapine-induced weight gain.     

首发精神分裂症患者代谢异常分析及奥氮平对其影响

目的 探讨首发精神分裂症患者代谢异常的情况及非典型抗精神病药物奥氮平对此可能的影响.方法 选取中山大学附属第三医院心理科自2010年2月至2011年2月收治的30例首发精神分裂症患者(病例组,予以奥氮平单药治疗4周)及40例健康者(对照组),分别在治疗前(基线)、后测定身高、体质量、腰围、臀围、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、载脂蛋白AI(aPOAI)、载脂蛋白B100(aPOB100)、脂蛋白a(LPa)、空腹血糖(FBS)、空腹胰岛素(INS)及C肽,计算胰岛素抵抗指数(Ⅱ)、腰臀比(WHR)和体重指数(BMI),并将病例组与对照组、病例组治疗前后各项代谢指标进行比较分析.结果 病例组HDL、aPOAI明显低于对照组,腰臀比、IR、INS、C肽明显高于对照组,差异均有统计学意义(P＜0.05).病例组治疗后BMI、腰围、腰臀比、胰岛素、IR、TC、TG、LDL、aPOB 100较治疗前均有明显增高,差异均有统计学意义(P＜0.05).结论 精神分裂症患者本身可能存在某些代谢异常的易感素质,其高代谢异常发生率可能是其易感素质与抗精神病药物共同作用的结果.     

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Background: The second-generation antipsychotic drug olanzapine is an effective pharmacological treatment for psychosis. However, use of the drug is commonly associated with a range of metabolic side effects, including glucose intolerance and insulin resistance. These symptoms have been accurately modelled in rodents. Methods: We compared the effects of 3 distinct classes of antidiabetic drugs, metformin (100 and 500 mg/kg, oral), rosiglitazone (6 and 30 mg/kg, oral) and glyburide (2 and 10 mg/kg, oral), on olanzapineinduced metabolic dysregulation. After acutely treating female rats with lower (7.5 mg/kg) or higher (15 mg/kg) doses of olanzapine, we assessed glucose intolerance using the glucose tolerance test and measured insulin resistance using the homeostatic model assessment of insulin resistance equation. Results: Both doses of olanzapine caused pronounced glucose dysregulation and insulin resistance, which were significantly reduced by treatment with metformin and rosiglitazone; however, glucose tolerance did not fully return to control levels. In contrast, glyburide failed to reverse the glucose intolerance caused by olanzapine despite increasing insulin levels. Limitations: We evaluated a single antipsychotic drug, and it is unknown whether other antipsychotic drugs are similarly affected by antidiabetic treatments. Conclusion: The present study indicates that oral hypoglycemic drugs that influence hepatic glucose metabolism, such as metformin and rosiglitazone, are more effective in regulating olanzapine-induced glucose dysregulation than drugs primarily affecting insulin release, such as glyburide. The current model may be used to better understand the biological basis of glucose dysregulation caused by olanzapine and how it can be reversed.