Mechanism of Action

Saxenda® (liraglutide Injection 3 mg) is the first GLP-1 analogue that is EMA and FDA approved for weight management as an adjunct to diet and exercise both in adults and adolescents (12-17 years) with obesity. One pre-filled Saxenda^® pen contains 18 mg liraglutide in 3 ml.¹

Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) analogue with 97% amino acid sequence homology to endogenous human GLP-1. Liraglutide binds to and activates the GLP-1 receptor (GLP-1R).GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action is not entirely clear.

In animal studies, peripheral administration of liraglutide led to uptake in specific brain regions involved in regulation of appetite, where liraglutide, via specific activation of the GLP-1R, increased key satiety and decreased key hunger signals, thereby leading to lower body weight.

GLP-1 receptors are also expressed in specific locations in the heart, vasculature, immune system and kidneys. In mouse models of atherosclerosis, liraglutide prevented aortic plaque progression and reduced inflammation in the plaque. In addition, liraglutide had a beneficial effect on plasma lipids.¹

* Saxenda^® is the result of 2 structural modifications to natural GLP-1 that prolong its half-life from less than 2 minutes to approximately 13 hours, when injected subcutaneously, allowing for once-daily dosing.^4,5

1. Saxenda^® Summary of Product Characteristics (Prescribing Information)

2. Orskov C, Wettergren A, Holst JJ. Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol. 1996;31(7):665-670.

3. Secher A, Jelsing J, Baquero AF, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014;124(10):4473-4488.

4. Jacobsen LV, Flint A, Olsen AK, Ingwersen SH. Liraglutide in type 2 diabetes mellitus: clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2016;55:657-672.

5. Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem. 2000;43(9):1664-1669.