Recent advances in fibroblast growth factor 21 (FGF21) biology and pharmacology have led to the development of several long-acting FGF21 analogues and antibody-based mimetics now in various phases of clinical trials for the treatment of obesity-related metabolic comorbidities. The efficacy of these FGF21 analogues/mimetics on glycaemic control and weight loss is rather mild and inconsistent; nevertheless, several promising therapeutic benefits have been reproducibly observed in most clinical studies, including amelioration of dyslipidaemia (particularly hypertriglyceridaemia) and hepatic steatosis, reduction of biomarkers of liver fibrosis and injury, and resolution of metabolic dysfunction-associated steatohepatitis (MASH). Evidence is emerging that combination therapy with FGF21 analogues and other hormones (such as glucagon-like peptide 1; GLP-1) can synergise their pharmacological benefits, thus maximising the therapeutic efficacy for obesity and its comorbidities.

中文翻译：

---

FGF21类似物临床试验现状及未来展望

成纤维细胞生长因子 21 (FGF21) 生物学和药理学的最新进展导致了几种长效 FGF21 类似物和基于抗体的模拟物的开发，目前正处于治疗肥胖相关代谢合并症的临床试验的各个阶段。这些 FGF21 类似物/模拟物对血糖控制和体重减轻的功效相当轻微且不一致；尽管如此，在大多数临床研究中已经重复观察到了一些有希望的治疗益处，包括改善血脂异常（特别是高甘油三酯血症）和肝脂肪变性、减少肝纤维化和损伤的生物标志物以及解决代谢功能障碍相关的脂肪性肝炎（MASH）。越来越多的证据表明，FGF21 类似物和其他激素（例如胰高血糖素样肽 1；GLP-1）的联合治疗可以协同其药理作用，从而最大限度地提高肥胖及其合并症的治疗效果。