Liraglutide is a potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and a synthetic derivative of GLP-1 (7-37) that contains a palmitic acid group.1 It increases cAMP accumulation in CHO cells expressing the human GLP-1 receptor (EC50 = 61 pM). Liraglutide (100-1,000 nM) inhibits cytokine- and free fatty acid-induced apoptosis of primary neonatal rat pancreatic β-cells in vitro by greater than 95 and 50%, respectively, effects that are blocked by the GLP-1 receptor antagonist exendin-3 (9-39) and the PI3 kinase inhibitor wortmannin.2 In a rat model of obesity induced by supplemental dietary candy, liraglutide (0.2 mg/kg, s.c., twice per day) decreases calorie intake, shifts food preference to a higher ratio of chow to candy, reverses weight and fat gains, and increases insulin sensitivity.3 Formulations containing liraglutide have been used as adjuncts in the treatment of type 2 diabetes and for chronic weight management in overweight or obese adults.
References:
[1]. Knudsen, L.B., Nielsen, P.F., Huusfeldt, P.O., et al.Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administrationJ. Med. Chem.43(9)1664-1669(2000).
[2]. Bregenholt, S., M?ldrup, A., Blume, N., et al.The long-acting glucagon-like peptide-1 analogue, liraglutide, inhibits beta-cell apoptosis in vitroBiochem. Bioph. Res. Commun.330(2)577-584(2005).
[3]. Raun, K., von Voss, P., Gotfredsen, C.F., et al.Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does notDiabetes56(1)8-15(2007).
















