Incidence of Newly Diagnosed Diabetes Attributable to Atypical Antipsychotic Medications

Department of Psychiatry, Yale University, New Haven, Connecticut, United States
American Journal of Psychiatry (Impact Factor: 12.3). 10/2004; 161(9):1709-11. DOI: 10.1176/appi.ajp.161.9.1709
Source: PubMed


The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis.
Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis.
Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine).
Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.

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    • "Atypical antipsychotic agents are first-line therapy for symptoms of schizophrenia and other psychotic disorders. However, numerous studies have documented a higher incidence of diabetes and hyperglycemia among patients treated with atypical antipsychotics (at least partially attributed to effects of weight gain) compared to typical agents (Caro et al., 2002; Koller and Doraiswamy, 2002; Kornegay et al., 2002; Koro et al., 2002; Sernyak et al., 2002; Buse et al., 2003; Gianfrancesco et al., 2003a, 2003b; Lindenmayer et al., 2003; Citrome et al., 2004; Leslie and Rosenheck, 2004; Gianfrancesco et al., 2006; Ramaswamy et al., 2006; DuMouchel et al., 2008; Smith et al., 2008). In addition, case reports and case series have suggested that these drugs may also have acute hyperglycemic effects, occasionally leading to diabetic ketoacidosis (DKA), coma, and death (Muench and Carey, 2001; Roefaro and Mukherjee, 2001; Jin et al., 2002; Koller et al., 2003; Wilson et al., 2003; Koller et al., 2004; Takahashi et al., 2005; Marlowe et al., 2007; Kohen et al., 2008; Makhzoumi et al., 2008). "
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    ABSTRACT: Objective To evaluate the relationship between initiation of atypical antipsychotic agents and the risk of hyperglycemic emergencies. Method We conducted a multicentre retrospective cohort study using administrative health data from 7 Canadian provinces and the UK Clinical Practice Research Datalink. Hospitalizations for hyperglycemic emergencies (hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state) were compared between new users of risperidone (reference), and new users of olanzapine, other atypical antipsychotics, and typical antipsychotics. We used propensity scores with inverse probability of treatment weighting and proportional hazard models to estimate the site-specific hazard ratios of hyperglycemic emergencies in the year following drug initiation separately for adults under and over age 66 years. Site-level results were pooled using meta-analytic methods. Results Among 725,489 patients, 55% were aged 66 + years; 5% of younger and 19% of older patients had pre-existing diabetes. Hyperglycemic emergencies were rare (1–2 per 1000 person years), but more frequent in patients with pre-existing diabetes (6–12 per 1000 person years). We did not find a significant difference in risk of hyperglycemic emergencies with initiation of olanzapine versus risperidone; however heterogeneity existed between sites. The risk of an event was significantly lower with other atypical (99% quetiapine) compared to risperidone use in older patients [adjusted hazard ratio, 95% confidence interval (CI): 0.69, 0.53–0.90]. Conclusions Risk for hyperglycemic emergencies is low after initiation of antipsychotics, but patients with pre-existing diabetes may be at greater risk. The risk appeared lower with the use of quetiapine in older patients, but the clinical significance of the findings requires further study.
    Full-text · Article · Apr 2014 · Schizophrenia Research
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    • "Olanzapine subjects had a higher rate of new-onset DM than that reported in a previous study: 7.3% over a 12–24 month follow-up period (Leslie and Rosenheck, 2004). This difference may in part be due to the high prevalence of pre-existing obesity in study subjects increasing DM risk. "

    Full-text · Chapter · Nov 2011
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    • "ns in the CHRM3 gene (Gautam et al. 2006). This might indicate that antagonism of the β-cell M3 receptor leads to a higher risk of hyperglycemia and developing diabetes in humans. Olanzapine and clozapine, which have the highest binding affinities with the M3 receptor, have been associated with highest risk of developing T2DM (Citrome et al. 2004; Leslie and Rosenheck. 2004; Holt et al. 2005; Newcomer. 2005) and higher levels of glycated hemoglobin (HBA1c) and blood glucose (Lieberman et al. 2005; Gianfrancesco et al. 2006; Nasrallah. 2008). Risperidone, quetiapine, ziprasidone , haloperidol, and aripiprazole have weak to absent M3 receptor antagonistic activity (Roth et al. 2004; Nasrallah. 2008) and are "
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    ABSTRACT: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. A significant association of interaction between haplotype rs346074-rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics.
    Full-text · Article · Feb 2011 · Psychopharmacology
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