CMAJ：二甲双胍或和患者机体促甲状腺激素水平下降直接相关

近日，刊登在国际杂志Canadian Medical Association Journal（CMAJ）上的一篇研究论文中，来自麦基尔大学的科学家通过研究表示，一种常用于治疗II型糖尿病的药物二甲双胍（Metformin）或许会增加甲状腺功能减退病人机体促甲状腺激素（TSH）水平下降的风险。

二甲双胍通常可以通过减少肝脏葡萄糖的产生来降低血糖水平，然而此前有研究表明，二甲双胍或许会降低机体促甲状腺激素（TSH）的水平。

这项研究中，研究者对接受二甲双胍和磺酰脲（另一种常用的糖尿病药物）治疗的74300名患者超过25年的研究数据进行分析，在这些个体中有5689名患者用于治疗甲状腺功能减退，59937名患者的甲状腺功能正常；在甲状腺功能减退患者组中，每年有495名患者会出现促甲状腺激素水平的降低，发生率为119.7/1000，而正常组的发生人数为322人，发生率为4.5/1000。

在治疗甲状腺功能减退的患者组中，相比磺酰脲疗法来讲，二甲双胍单一疗法会增加患者55%的促甲状腺激素水平下降的风险，而二甲双胍疗法并不会影响甲状腺功能正常的个体。研究者Laurent Azoulay表示，我们进行本文纵向调查的研究结果显示，二甲双胍的使用和治疗甲状腺功能减退患者机体促甲状腺激素水平下降的风险直接相关，未来研究中我们将会通过临床试验研究来评估这种效应。（转化医学网360zhyx.com）

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Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus
CMAJ doi: 10.1503/cmaj.140688
Jean-Pascal Fournier, Hui Yin, Oriana Hoi Yun Yu, Laurent Azoulay
Background: Small cross-sectional studies have suggested that metformin, a first-line oral hypoglycemic agent, may lower thyroid-stimulating hormone (TSH) levels. Our objective was to determine whether the use of metformin monotherapy, when compared with sulfonylurea monotherapy, is associated with an increased risk of low TSH levels (< 0.4 mIU/L) in patients with type 2 diabetes mellitus.
Methods: Using the Clinical Practice Research Datalink, we identified patients who began receiving metformin or sulfonylurea monotherapy between Jan. 1, 1988, and Dec. 31, 2012. We assembled 2 subcohorts of patients with treated hypothyroidism or euthyroidism, and followed them until Mar. 31, 2013. We used Cox proportional hazards models to evaluate the association of low TSH levels with metformin monotherapy, compared with sulfonylurea monotherapy, in each subcohort.
Results: A total of 5689 patients with treated hypothyroidism and 59 937 euthyroid patients were included in the subcohorts. Among patients with treated hypothyroidism, 495 events of low TSH levels were observed during follow-up (incidence rate 119.7/1000 person-years). In the euthyroid group, 322 events of low TSH levels were observed (incidence rate 4.5/1000 person-years). Compared with sulfonylurea monotherapy, metformin monotherapy was associated with a 55% increased risk of low TSH levels in patients with treated hypothyroidism (incidence rate 79.5/1000 person-years v.125.2/1000 person-years, adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.09–2.20), with the highest risk in the 90–180 days after initiation (adjusted HR 2.30, 95% CI 1.00–5.29). No association was observed in euthyroid patients (adjusted HR 0.97, 95% CI 0.69–1.36).
Interpretation: In this longitudinal population-based study, metformin use was associated with an increased incidence of low TSH levels in patients with treated hypothyroidism, but not in euthyroid patients. The clinical consequences of this need further investigation.