Dan Siskind, Anthony W Russell, Shuichi Suetani, Dylan Flaws, Steve Kisely, Vikas Moudgil, Korinne Northwood, Gail Robinson, James G Scott, Terry Stedman, Nicola Warren, Karl Winckel, Peter Cosgrove, Andrea Baker
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Secondary outcomes included comparative rates of weight gain of more than 5%, overall weight gain/loss, and differences in metabolic and psychosis outcomes.</p><p><strong>Results: </strong>The study was closed prematurely in March 2020 due to COVID-19 restrictions. Ten participants were randomised to each of the metformin and placebo groups. Eight metformin group and five placebo group participants completed the trial and were included in the analysis. The study was insufficiently powered to detect difference between the metformin and placebo groups for the primary outcome of change in weight (0.09 kg vs 2.88 kg, <i>p</i> = 0.231). In terms of secondary outcomes, people in the metformin group were significantly less likely to gain >5% of their body weight (12.5% vs 80%, <i>p</i> = 0.015) and were more likely to lose weight (37.5% vs 0% <i>p</i> = 0.024) compared to placebo. 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引用次数: 5
摘要
背景：在氯氮平开始使用时，干预措施可最大限度地减少体重增加的证据有限。我们比较了氯氮平初始阶段二甲双胍与安慰剂的辅助治疗效果。方法：开始服用氯氮平的精神分裂症患者随机接受二甲双胍或安慰剂治疗24天 周。主要结果是体重变化的差异。次要结果包括体重增加超过5%的比较率、总体体重增加/减少以及代谢和精神病结果的差异。结果：由于新冠肺炎限制，该研究于2020年3月提前关闭。10名参与者被随机分为二甲双胍组和安慰剂组。八名二甲双胍组和五名安慰剂组参与者完成了试验并纳入分析。该研究不足以检测二甲双胍组和安慰剂组之间体重变化的主要结果差异（0.09 kg vs 2.88 kg，p = 0.231）。就次要结果而言，二甲双胍组患者体重增加>5%的可能性显著降低（12.5%对80%，p = 0.015），并且更有可能减肥（37.5%vs0%p = 0.024）。两组之间在药物不良反应（ADR）方面没有差异。结论：尽管受新冠肺炎导致试验被迫提前结束的限制，19但这项随机对照试验的结果是有希望的。氯氮平和二甲双胍联合用药可能是预防氯氮平相关体重增加的一种有前景的治疗方法，特别是考虑到二甲双胍相关的不良反应发生率较低。这支持了使用二甲双胍预防氯氮平患者体重增加的考虑；然而，还需要进一步的研究来证实这一发现。试验注册号：ACTRN12617001547336。
CoMET: a randomised controlled trial of co-commencement of metformin versus placebo as an adjunctive treatment to attenuate weight gain in patients with schizophrenia newly commenced on clozapine.
Background: There is limited evidence on interventions to minimise weight gain at clozapine commencement. We compared the effect of adjunctive metformin versus placebo at clozapine initiation.
Methods: People with schizophrenia commencing on clozapine were randomised to either metformin or placebo for 24 weeks. The primary outcome was difference in the change of body weight. Secondary outcomes included comparative rates of weight gain of more than 5%, overall weight gain/loss, and differences in metabolic and psychosis outcomes.
Results: The study was closed prematurely in March 2020 due to COVID-19 restrictions. Ten participants were randomised to each of the metformin and placebo groups. Eight metformin group and five placebo group participants completed the trial and were included in the analysis. The study was insufficiently powered to detect difference between the metformin and placebo groups for the primary outcome of change in weight (0.09 kg vs 2.88 kg, p = 0.231). In terms of secondary outcomes, people in the metformin group were significantly less likely to gain >5% of their body weight (12.5% vs 80%, p = 0.015) and were more likely to lose weight (37.5% vs 0% p = 0.024) compared to placebo. There was no difference between the groups in terms of adverse drug reactions (ADRs).
Conclusion: While limited by the forced premature closure of the trial due to COVID19, the findings from this randomised controlled trial are promising. Clozapine and metformin co-commencement may be a promising treatment to prevent clozapine-associated weight gain, especially given the low rates of ADRs associated with metformin. This supports the consideration of use of metformin to prevent weight gain in people initiated on clozapine; however, further studies are needed to confirm this finding.
期刊介绍：
Therapeutic Advances in Psychopharmacology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of psychopharmacology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in psychopharmacology, providing a forum in print and online for publishing the highest quality articles in this area.
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