二甲双胍治疗抗精神病药物引起的血脂异常:两项随机、安慰剂的对照研究

目的：验证二甲双胍治疗抗精神病药引起的血脂异常的疗效和安全性。方法：将两项随机、安慰剂的 对照研究纳入分析。共有201例服用抗精神病药物后出现血脂异常的首发精神分裂症患者，并将其分为1 000 mg/d 二甲双胍组(以下简称为二甲双胍组，n=103)和安慰剂组(n=98)，观察24周。在基线、治疗后第12周和第24周进行 临床症状及体重、血糖、血脂等代谢指标的评估。结果：二甲双胍治疗后，二甲双胍组和安慰剂组之间低密度脂 蛋白胆固醇(low density lipoprotein cholesterol，LDL-C)的平均差异从基线时的0.16 mmol/L，降低到第24周结束时的 –0.86 mmol/L，降低了1.02 mmol/L，差异有统计学意义(P<0.01)。而24周结束时，二甲双胍组LDL-C≥3.37 mmol/L的 患者有25.3%，显著低于安慰剂组24周结束时的64.8%(P<0.01)。与安慰剂组相比，二甲双胍组的体重、体重指数、 胰岛素、胰岛素抵抗指数、总胆固醇、三酰甘油和高密度脂蛋白胆固醇也有显著变化，差异均有统计学意义(均 P<0.05)。治疗对体重和胰岛素抵抗的影响出现在第12周，并且在第24周进一步改善，但对改善血脂异常的作用在第 24周结束时才出现。结论：二甲双胍治疗对于改善抗精神病药物引起的血脂异常和胰岛素抵抗是有效的，并且改善 抗精神病药物诱导的胰岛素抵抗出现的时间早于降低血脂异常的时间。

Metformin treatment of antipsychotic-induced dyslipidemia: analysis of two randomized,placebo-controlled trials

Objective: To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia. Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively. Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to –0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L (P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week. Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.