Metformin reduces autoimmune antibody levels in patients with Hashimoto’s thyroiditis: A systematic review and meta-analysis

In the past few years, an increasing number of studies have proposed the idea of extending the therapeutic range of metformin from traditional hypoglycaemic to autoimmune diseases, and confirmed in a variety of autoimmune diseases. However, whether metformin can be used to treat Hashimoto’s thyroiditis (HT), which is characterised by thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), is unknown. Therefore, we conducted a systematic review and meta-analysis to evaluate whether metformin can reduce the levels of TPOAb and TgAb in patients with HT or subclinical hypothyroidism (SH), so as to provide a theoretical basis for metformin treatment of these diseases. PubMed, Web Of Science and Embase were searched for observational studies investigating the changes of TPOAb and TgAb in patients with HT after metformin treatment. Two authors extracted data from eligible studies and classified them as HT and subclinical hypothyroidism subgroups. The calculation was then performed by weighted mean difference (WMD) combined with a fixed-effects model analysis or standard mean difference (SMD) with a random-effects model analysis, based on the measurement of the outcome. Metformin significantly reduced TPOAb levels and TgAb levels in patients with HT and SH, especially TPOAb (HT: <i>p</i> _TPOAb = .009, <i>p</i> _TgAb = .046; SH: <i>p</i> _TPOAb = .034, <i>p</i> _TgAb = .066). In addition, metformin also reduced the levels of thyroid stimulating hormone (TSH), homeostasis model assessment of insulin resistance (HOMA-IR) in patients with HT and SH (HT: <i>p</i> _TSH = .000 and <i>p</i> _HOMA-IR = .000; SH: <i>p</i> _TSH = .000 and <i>p</i> _HOMA-IR = .000, respectively). Metformin significantly reduces TPOAb level and TgAb level in patients with HT and SH, especially TPOAb. This study is the first to provide a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.

近年来，越来越多的研究提出将二甲双胍的治疗范围从传统降糖领域拓展至自身免疫性疾病，并在多种自身免疫性疾病中得到验证。然而，二甲双胍能否用于治疗以甲状腺过氧化物酶抗体（thyroid peroxidase antibody, TPOAb）和甲状腺球蛋白抗体（thyroglobulin antibody, TgAb）升高为特征的桥本甲状腺炎（Hashimoto’s thyroiditis, HT），目前尚不清楚。因此，本研究开展系统评价与荟萃分析，旨在评估二甲双胍是否可降低桥本甲状腺炎或亚临床甲状腺功能减退症（subclinical hypothyroidism, SH）患者的TPOAb与TgAb水平，为二甲双胍治疗此类疾病提供理论依据。本研究检索PubMed、Web Of Science及Embase数据库，筛选有关二甲双胍治疗后HT患者TPOAb与TgAb水平变化的观察性研究。由两名研究者独立提取符合纳入标准的研究数据，并按HT与SH两个亚组进行分类。随后根据结局指标的测量类型，分别采用加权均数差（weighted mean difference, WMD）结合固定效应模型分析，或标准均数差（standard mean difference, SMD）结合随机效应模型分析进行数据合并。分析结果显示，二甲双胍可显著降低HT与SH患者的TPOAb与TgAb水平，其中对TPOAb的改善效果尤为明显（HT组：<i>p</i>_TPOAb = 0.009，<i>p</i>_TgAb = 0.046；SH组：<i>p</i>_TPOAb = 0.034，<i>p</i>_TgAb = 0.066）。此外，二甲双胍还可降低HT与SH患者的促甲状腺激素（thyroid stimulating hormone, TSH）、胰岛素抵抗稳态模型评估（homeostasis model assessment of insulin resistance, HOMA-IR）水平（HT组：<i>p</i>_TSH = 0.000，<i>p</i>_HOMA-IR = 0.000；SH组：<i>p</i>_TSH = 0.000，<i>p</i>_HOMA-IR = 0.000）。综上，二甲双胍可显著降低HT与SH患者的TPOAb与TgAb水平，尤以TPOAb改善效果显著。本研究首次为二甲双胍临床应用于HT治疗提供了初步理论依据。