Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study

Wu, Renhua; Zhao, Jingping; Guo, Xiaofeng; He, Yanling; Fang, Maosheng; Guo, Wenbin; Chen, Jindong; Li, Lehua

doi:10.1176/appi.ajp.2007.07010079

Cited by 193 publications

(168 citation statements)

References 40 publications

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“…Eleven double blind, randomized, controlled trials have examined Met in this role (Baptista et al 2006, Klein et al 2006, Arman et al 2008, Wu et al 2008a,b, 2012, Carrizo et al 2009, Chen et al 2013, Jarskog et al 2013. Of these, nine examined a surrogate measure of insulin sensitivity, the homeostasis model assessment of insulin resistance (HOMA-IR), with six demonstrating beneficial effects favoring Met (Wu et al 2008a,b, Carrizo et al 2009, Chen et al 2013, Jarskog et al 2013.…”

Section: Introductionmentioning

confidence: 99%

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Remington

Teo

Wilson

et al. 2015

Journal of Endocrinology

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Antipsychotics (APs) are linked to diabetes, even without weight gain. Whether anti-diabetic drugs are efficacious in reversing the direct effects of APs on glucose pathways is largely undetermined. We tested two metformin (Met) doses to prevent impairments seen following a dose of olanzapine (Ola) (3 mg/kg); glucokinetics were measured using the hyperinsulinemic-euglycemic clamp (HIEC). Met (150 mg/kg; nZ13, or 400 mg/kg; nZ11) or vehicle (Veh) (nZ11) was administered through gavage preceding an overnight fast, followed by a second dose prior to the HIEC. Eleven additional animals were gavaged with Veh and received a Veh injection during the HIEC (Veh/Veh); all others received Ola. Basal glucose was similar across treatment groups. The Met 400 group had significantly greater glucose appearance (R a ) in the basal period (i.e., before Ola, or hyperinsulinemia) vs other groups. During hyperinsulinemia, glucose infusion rate (GINF) to maintain euglycemia (reflective of whole-body insulin sensitivity) was higher in Veh/Veh vs other groups. Met 150/Ola animals demonstrated increased GINF relative to Veh/Ola during early time points of the HIEC. Glucose utilization during hyperinsulinemia, relative to basal conditions, was significantly higher in Veh/Veh vs other groups. The change in hepatic glucose production (HGP) from basal to hyperinsulinemia demonstrated significantly greater decreases in Veh/Veh and Met 150/Ola groups vs Veh/Ola. Given the increase in basal R a with Met 400, we measured serum lactate (substrate for HGP), finding increased levels in Met 400 vs Veh and Met 150. In conclusion, Met attenuates hepatic insulin resistance observed with acute Ola administration, but fails to improve peripheral insulin resistance. Use of supra-therapeutic doses of Met may mask metabolic benefits by increasing lactate.

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Section: Introductionmentioning

confidence: 99%

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Remington

Teo

Wilson

et al. 2015

Journal of Endocrinology

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“…Klein and colleagues, in their randomized, double-blind, placebo-controlled trial of metformin in children and adolescents taking atypical antipsychotics, found arrested weight gain, as well as improved insulin resistance (Klein et al 2006). Whereas Baptista and associates found that metformin did not prevent olanzapineinduced weight gain in a group of adult patients with schizophrenia (Baptista et al 2006), Wu and colleagues published two studies indicating that metformin, administered to a group of adult patients with schizophrenia on antipsychotics, including olanzapine, was effective in attenuating weight gain and improving insulin sensitivity (Wu et al 2008a;Wu et al 2008b). …”

Section: Introductionmentioning

confidence: 99%

Metformin for Weight Control in Pediatric Patients on Atypical Antipsychotic Medication

Shin

Bregman

Breeze

et al. 2009

Journal of Child and Adolescent Psychopharmacology

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Objective: Metformin was assessed as an interventional medication for weight gain in children and adolescents taking atypical antipsychotic agents. Method: A 12-week open-label trial was conducted to evaluate metformin's effectiveness and safety for weight management. Eleven subjects, ages 10-18 years, participated in the study. Each subject received metformin orally up to 2000 mg=day. Primary outcome measures included weight, body mass index (BMI), and waist circumference. Secondary outcome measures included serum glucose, insulin, and fasting lipid profile. Changes in weight, BMI, waist, and metabolic profile were obtained by using repeated measures of covariance. Results: The mean reduction in weight, waist, BMI, serum glucose, and serum insulin was not statistically significant. However, 5 out of 11 patients lost weight (mean, À2.82 kg AE 7.25), and overall the sample did not continue to gain weight. There was a significant decrease in triglyceride levels. Metformin was fairly well tolerated. Conclusion: Preliminary data suggests that metformin may safely and effectively improve the triglyceride profile. However, contrary to study hypotheses, weight, waist, and BMI reduction were not statistically significant. Future double-blind studies with larger sample sizes and of longer duration are warranted to assess more fully the safety and efficacy of this intervention.

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“…Evidence indicates that metabolic profile of antipsychotics varies, therefore resulting in some having greater propensity than others to cause hyperglycemia [29,30]. However, clinicians need to consider the overall wellbeing of an individual and finely balance out improvements in mental health against physical health complications.…”

Section: Discussionmentioning

confidence: 99%

Lester Adaptation of Cardio Metabolic Measurements: An Inpatient Interventional Framework for Women with Mental Illness

M¹,

Lotfy²,

L³

2017

Endocrinol Metab Syndr

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Aims of the study: To assess the prevalence of metabolic syndrome and implement a framework for screening and management of cardio metabolic risks in women on psychiatric in-patient wards.Background: An estimated 29-48% of psychiatric in-patients have metabolic syndrome. Severe mood disorders and psychotic illnesses are independent risk factors. 20-25% of the world's adult population have metabolic syndrome and they are twice as likely to die from and three times as likely to have a heart attack or stroke compared with people without the syndrome. This study gives an overview of the application of Lester Tool on busy in-patient units and interventional approaches adapted by the team.

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Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study

Abstract: 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.

Cited by 193 publications

References 40 publications

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Metformin for Weight Control in Pediatric Patients on Atypical Antipsychotic Medication

Lester Adaptation of Cardio Metabolic Measurements: An Inpatient Interventional Framework for Women with Mental Illness

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