Abstract: The invention relates to methods and compositions for reducing blood glucose levels in hyperglycaemic subjects. The methods and compositions may therefore be suitable for treating a disease or condition associated with hyperglycaemia such as, for example, obesity (particularly diet induced obesity (DIO)), weight gain, Type II diabetes mellitus, insulin sensitivity, impaired glucose tolerance and inflammation. In some embodiments, the methods comprise administering a melanocortin-5 receptor (MC5R) agonist to one or more skeletal muscle cells of the subject. Preferred MC5R agonists are those that specifically activate MC5R and/or enhance expression of MC5R, such as the melanocortin analogue, Ac-Nle-c[Asp-Pro-D-Nal(2?)-Arg-Trp-Lys]-NH2.