Abstracto

Liraglutide: a human GLP-1 analog for Type 2 diabetes

Tina Vilsboll

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the intestinal mucosa in response to nutrient ingestion. Although GLP-1 has multiple potentially benefi cial effects, it is unsuitable as a therapy in Type 2 diabetes due to its short half-life. Liraglutide is an analog of human GLP-1 with high (97%) sequence homology, but has protracted pharmacokinetics as a result of aggregation at its injection site, albumin binding in the circulation and reduced susceptibility to enzymatic degradation. Liraglutide has glucose-lowering effects spanning 24 h, with improvements in fasting and postprandial glucose levels. In clinical studies, liraglutide has achieved reductions in HbA1c of up to 1.6% when used as monotherapy in drug-naive subjects. The incidence of hypoglycemia with liraglutide treatment is relatively low, perhaps refl ecting a glucose dependency of its insulinotropic action. Liraglutide also has clinically relevant effects on body weight, with mean reductions of 2–3 kg occurring in large clinical trials. Additionally, data are suggesting benefi cial effects on cardiovascular risk factors: systolic blood pressure is reduced by 2–6 mmHg with liraglutide treatment, while Phase II studies have demonstrated improvements in molecular markers of cardiovascular risk. Treatment with liraglutide also appears to have effects on β-cell function, with clinical data showing improvements in β-cell function and insulin secretory capacity. The signifi cance of animal data suggesting benefi cial effects of liraglutide on β-cell mass and apoptosis have not been confi rmed in humans. The most common adverse event during liraglutide treatment is nausea; this is experienced initially by a minority of subjects, but decreases to relatively low levels with continued treatment.