Fan Cheng, Huang Shiyuan, Xiang Chunhua, Song Yi
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Medicine (Baltimore). 2025 Jun 20;104(25):e42880. doi: 10.1097/MD.0000000000042880.
Sarcopenia is prevalent among elder patients with type 2 diabetes. As a first-line medication for managing type 2 diabetes, metformin has shown controversial effects on sarcopenia. This study aims to analyze the impact of metformin on sarcopenia using Mendelian randomization analysis. We selected 30 single nucleotide polymorphisms associated with metformin used as instrumental variables from genome-wide association studies. Mendelian randomization was conducted using inverse variance weighted (IVW), Mendelian randomization Egger, and weighted median methods. Additionally, we performed heterogeneity tests, Pleiotropy analyses, and sensitivity analyses to validate our findings. The IVW method indicated a P-value of .63 and an odds ratio (OR) of 0.93 (95% CI: 0.69-1.25) for the relationship between metformin use and walking pace. For appendicular lean mass, the IVW method showed a P-value of .42 and an OR of 0.69 (95% CI: 0.28-1.70). In contrast, the IVW analysis indicated a significant relationship between metformin use and right hand grip strength, with P-value of .01 and OR (95% CI) = 0.64 (0.45-0.91), as well as for left hand grip strength, with P-value of .01 and OR (95% CI) = 0.65 (0.45-0.92). Notably, a causal relationship was established between metformin use and lower hand grip strength, while no causal relationship was found between metformin use and walking pace or appendicular lean mass. This study suggests that caution is needed regarding long-term metformin use in the context of sarcopenia.
肌肉减少症在老年2型糖尿病患者中普遍存在。作为治疗2型糖尿病的一线药物，二甲双胍对肌肉减少症的影响存在争议。本研究旨在使用孟德尔随机化分析来分析二甲双胍对肌肉减少症的影响。我们从全基因组关联研究中选择了30个与二甲双胍相关的单核苷酸多态性作为工具变量。使用逆方差加权（IVW）、孟德尔随机化Egger和加权中位数方法进行孟德尔随机化。此外，我们进行了异质性检验、多效性分析和敏感性分析以验证我们的发现。IVW方法显示，二甲双胍使用与步行速度之间的关系的P值为0.63，比值比（OR）为0.93（95%CI：0.69-1.25）。对于四肢瘦体重，IVW方法显示P值为0.42，OR为0.69（95%CI：0.28-1.70）。相比之下，IVW分析表明，二甲双胍使用与右手握力之间存在显著关系，P值为0.01，OR（95%CI）=0.64（0.45-0.91），与左手握力之间也存在显著关系，P值为0.01，OR（95%CI）=0.65（0.45-0.92）。值得注意的是，二甲双胍使用与较低的握力之间建立了因果关系，而在二甲双胍使用与步行速度或四肢瘦体重之间未发现因果关系。本研究表明，在肌肉减少症的情况下，长期使用二甲双胍需要谨慎。
