Clozapine induces metformin-resistant prediabetes/diabetes that is associated with poor clinical efficacy in patients with early treatment-resistant schizophrenia

• Published in: Journal of affective disorders 2021-12, Vol.295, p.163-172
• Main Authors: Zhuo, Chuanjun, Xu, Yong, Wang, Haibo, Zhou, Chunhua, Liu, Jian, Yu, Xiaocui, Shao, Hailin, Tian, Hongjun, Fang, Tao, Li, Qianchen, Chen, Jiayue, Xu, Shuli, Ma, Xiaoyan, Yang, Weiliang, Yao, Cong, Li, Bo, Yang, Anqu, Chen, Yuhui, Huang, Guoyong, Lin, Chongguang
• Format: Article
• Language: English
• Subjects: Antipsychotic Agents - adverse effects; Clozapine; Clozapine - adverse effects; Diabetes; Humans; Metformin; Prediabetes; Prediabetic State - chemically induced; Prediabetic State - epidemiology; Prospective Studies; Schizophrenia; Schizophrenia - drug therapy; Treatment Outcome; Treatment-resistant schizophrenia
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2021.08.023

•The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in schizophrenia early-treatment resistance (E-TR) subtype.•Clozapine-induced metformin-resistant prediabetes/diabetes represented an independent risk factor that adversely affected the clinical efficacy of clozapine for schizophrenia E-TR subtype.•Switching to clozapine strategy should be reconsidered in the treatment of patients with schizophrenia E-TR subtype.•Given the high incidence of metformin-resistant clozapine-induced prediabetes/diabetes, the viability of lifestyle interventions to prevent clozapine-induced prediabetes/diabetes in patients with schizophrenia E-TR subtype should be assessed in future studies. Two distinct subtypes of treatment-resistant schizophrenia (TRS) have been recently reported, including early-treatment resistance (E-TR) and late-treatment resistance (L-TR). This study was to assess clozapine-induced metformin-resistant prediabetes/diabetes and its correlation with clinical efficacy in schizophrenia E-TR subtype. This prospective cohort study enrolled 230 patients with schizophrenia E-TR subtype and they were treated with adequate doses of clozapine for 16 weeks, during which patients with prediabetes/diabetes were assigned to receive add-on metformin. The main outcomes and measures included incidence of clozapine-induced prediabetes/diabetes and metformin-resistant prediabetes/diabetes, and the efficacy of clozapine as assessed by the Positive and Negative Syndrome Scale (PANSS) score. Clozapine-induced prediabetes/diabetes occurred in 76.52% of patients (170 prediabetes and 6 diabetes), of which the blood sugar of 43 (24.43%) patients was controlled with metformin. Despite add-on metformin, 47.06% (74/170) of prediabetes patients progressed to diabetes. In total, the incidence of clozapine-induced metformin-resistant prediabetes/diabetes was 75.57% (133/176). On completion of 16-week clozapine treatment, 16.52% (38/230) patients showed clinical improvement with PANSS scores of ≥50% declining. Furthermore, clozapine-induced prediabetes/diabetes was significantly correlated with the poor clinical efficacy of clozapine for schizophrenia E-TR subtype. The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in the schizophrenia E-TR subtype. Clozapine-induced metformin-resistant prediabetes/diabetes represents an independent risk factor that adversely affects the clinical efficacy of clo