Comparison of PEGylated FGF-21 with insulin glargine for long-lasting hypoglycaemic effect in db/db mice

Aim. - This study investigated the long-acting antidiabetic efficacy of PEGylated fibroblast growth factor (FGF)-21 in type 2 diabetic db/db mice. Methods. - PEGylated FGF-21 was prepared by modifying the N-terminus of human FGF-21 (hFGF-21) using mPEG-ALD. To compare the long-lasting hypoglycaemic effects of PEGylated FGF-21 and insulin glargine in diabetic db/db mice, their pharmacological efficacy was evaluated by changes in blood glucose levels, body weight, insulin levels, glycosylated haemoglobin levels, lipid profile and liver function parameters, and by oral glucose tolerance tests (OGTTs). Results. - Both PEGylated FGF-21 and insulin glargine decreased plasma glucose in db/db mice. However, compared with insulin glargine treatment, PEGylated FGF-21 therapy had more significant effects in lowering blood glucose and glycosylated haemoglobin levels, improving lipid profile and liver function parameters, alleviating insulin resistance and reducing the glucose area under the curve in OGTTs. Conclusion. - Our results suggest that PEGylated FGF-21 is an ideal candidate as a long-acting antidiabetes drug, and holds significant promise as an effective therapeutic agent in the treatment of type 2 diabetes patients. (C) 2014 Elsevier Masson SAS. All rights reserved.