Mechanism of action & pharmacodynamics

Nevolat^® is a chemcially synthesised glucagon-like peptide-1 receptor agonist (GLP-1 RA) with 97% sequence homology to human GLP-1 that binds to and activates the GLP-1 receptor. The GLP-1 receptor is the target for native GLP-1, an endogenous incretin hormone that amplifies glucose-dependent insulin secretion from the pancreatic beta cells and acts as a physiological regulator of appetite and food intake. Although 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. Via specific activation of the GLP-1R, liraglutide increased key satiety and decreased key hunger signals, thereby leading to a reduction in body weight.

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

Pharmacodynamic effects

Liraglutide lowers body weight in humans mainly through loss of fat mass with relative reductions in visceral fat being greater than for subcutaneous fat loss. Liraglutide regulates appetite by increasing feelings of fullness and satiety, while lowering feelings of hunger and prospective food consumption, thereby leading to reduced food intake. Liraglutide does not increase energy expenditure compared to placebo. Liraglutide stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent manner which results in a lowering of fasting and postprandial glucose. The glucose-lowering effect is more pronounced in patients with pre-diabetes and diabetes compared to patients with normoglycaemia. Clinical trials suggest that liraglutide improves and sustains beta-cell function, according to HOMA-B and the proinsulin-to-insulin ratio.¹