Liraglutide

Liraglutide marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.

Liraglutide is marketed under the brandname Victoza in the U.S. and Europe. It has been launched in Germany, Denmark, the Netherlands, the United Kingdom, Ireland, and the United States.

Cancer concerns

On April 2, 2009, an FDA advisory panel reviewed the significance of malignant C-cell carcinoma and thyroid C-cell focal hyperplasia in rats and mice. Some say the tumors were caused by a non-genotoxic, specific receptor-mediated mechanism to which rodents are particularly sensitive whereas non-human primates and humans are not. The Victoza label carries a Black Box Warning, "Because of the uncertain relevance of the rodent thyroid C-cell tumor findings to humans, prescribe Victoza only to patients for whom the potential benefits are considered to outweigh the potential risk". The FDA said that serum calcitonin, a biomarker of medulliary thyroid cancer, was slightly increased in liraglutide patients but still within normal ranges, and it required ongoing monitoring for 15 years in a cancer registry.

Pharmacodynamics

Studies to date suggest liraglutide improves control of blood glucose. It reduces meal-related hyperglycemia (for 12 hours after administration) by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

Liraglutide may have advantages over current therapies:

It acts in a glucose-dependent manner, meaning that it will stimulate insulin secretion only when blood glucose levels are higher than normal. Consequently, it shows negligible risk of hypoglycemia.
It has the potential for inhibiting apoptosis and stimulating regeneration of beta cells (seen in animal studies).
It decreases appetite and maintains body weight, as shown in a head-to-head study versus glimepiride.
It lowers blood triglyceride levels.
It has only mild and transient side effects, mainly gastrointestinal.

Pharmacokinetics

Liraglutide is a once-daily GLP-1 derivative for the treatment of type 2 diabetes. GLP-1, in its natural form, is short-lived in the body (the half-life after subcutaneous injection is approximately one hour), so it is not very useful as a therapeutic agent. However, liraglutide has a half-life after subcutaneous injection of 11–15 hours, making it suitable for once-daily dosing
The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at one position of the GLP-1 molecule, enabling it to bind to albumin within the subcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Binding with albumin also results in slower degradation and reduced elimination of liraglutide from the circulation by the kidneys compared to GLP-1