The invention relates to a derivative of a FGF21 protein having a cysteine residue at a position corresponding to position 167, 169, 170, 171, 172, 173, 174, 175 and in particular position 180 or position 181 of mature human FGF21 and derivatives thereof having a side chain attached to this cysteine. The FGF21 derivatives of the invention display high potency towards the FGF receptors. The invention also relates to pharmaceutical compositions comprising such FGF21 derivatives and pharmaceutically acceptable excipients, as well as the medical use of the FGF21 derivatives.本發明係關於在對應於成熟的人類FGF21之位置167、169、170、171、172、173、174、175且特別是位置180或位置181的位置具有半胱胺酸殘基的FGF21蛋白質之衍生物與其具有接附至此半胱胺酸的側鏈的衍生物。本發明之FGF21衍生物對FGF受體顯示高程度的效力。本發明亦係關於包含如此FGF21衍生物與醫藥上可接受的賦形劑的醫藥組成物、以及該FGF21衍生物之醫藥用途。