不同降糖药物对肌肉减少及骨代谢的影响

Effects of Different Antidiabetic Drugs on Sarcopenia and Bone Metabolism

摘要: 2型糖尿病(T2DM)患者常面临肌少症与骨质疏松症的双重威胁，而不同机制的降糖药物对“肌肉–骨骼系统”的影响存在显著异质性。本文系统评价了各类主流降糖药的肌骨效应及潜在机制，以期为临床提供兼顾肌骨健康的用药参考。综述发现，GLP-1受体激动剂(GLP-1RA)虽可能引起瘦体重减少，但能显著优化体成分比例，且对骨折风险总体呈中性；SGLT-2抑制剂(SGLT-2i)骨骼安全性总体良好，但需警惕体液减少引发的非代谢性跌倒风险；二甲双胍显示出潜在的抗衰老与肌骨保护作用；相比之下，噻唑烷二酮类药物(TZDs)因促进骨髓脂肪化明确增加骨折风险，应在骨折高危人群中避免使用；胰岛素治疗相关的骨折风险则主要归因于严重低血糖诱发的跌倒而非直接骨毒性。综上所述，T2DM的临床管理应高度关注药物的肌骨脱靶效应，建议根据患者的肌骨表型实施个体化选药，并结合生活方式干预以协同维护患者的代谢健康与肌骨功能。

Abstract: Patients with type 2 diabetes mellitus (T2DM) frequently face the dual threat of sarcopenia and osteoporosis. Antidiabetic drugs, with their diverse mechanisms, exert significantly heterogeneous effects on the “muscle-bone system”. This review systematically evaluates the musculoskeletal effects and underlying mechanisms of various mainstream antidiabetic agents, aiming to provide clinical guidance for pharmacotherapy that considers musculoskeletal health. The review found that glucagon-like peptide-1 receptor agonists (GLP-1RA), despite potentially causing a reduction in lean body mass, significantly optimize body composition ratios and have an overall neutral effect on fracture risk. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) generally exhibit good bone safety, but caution is warranted regarding non-metabolic falls induced by volume depletion. Metformin shows potential anti-aging and musculoskeletal protective effects. In contrast, thiazolidinediones (TZDs) are definitively associated with an increased risk of fractures due to the promotion of bone marrow adipogenesis and should be avoided in high-risk populations. The fracture risk associated with insulin therapy is primarily attributed to falls induced by severe hypoglycemia rather than direct skeletal toxicity. In summary, clinical management of T2DM should highly prioritize the off-target musculoskeletal effects of pharmacotherapy. Individualized drug selection based on the patient’s muscle-bone phenotype is recommended, alongside lifestyle interventions, to synergistically maintain metabolic health and musculoskeletal function.