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NMR structure of liraglutide. PDB entry 4apd
Clinical data
Trade names Victoza
Pregnancy cat.
Legal status
Routes oral, subcutaneous
CAS number 204656-20-2
ATC code A10BX07
PubChem CID 44147092
DrugBank DB06655
Chemical data
Formula C172H265N43O51
Mol. mass 3751.202

Liraglutide (NN2211), marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 agonist (GLP-1 agonist) developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.[1][2][3][4][5]

Liraglutide is marketed under the brandname Victoza in the U.S., India, Canada, Europe and Japan. It has been launched in Germany, Denmark, the Netherlands, the United Kingdom, Ireland, Sweden, Japan, Canada, the United States, France, Malaysia and Singapore.

Phase I trials of an oral variant of Victoza (NN9924) started in 2010.[6]


Studies to date suggest liraglutide improves control of blood glucose.[7]

It reduces meal-related hyperglycemia (for 24 hours after administration) by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) agonist, with a 97% amino acid sequence identity to endogenous human GLP-1(7-37). GLP-1(7-37) represents less than 20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP), leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying. GLP-1(7-37) has a half-life of 1.5–2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once daily administration, is a result of self-association that delays absorption, plasma protein binding and stability against metabolic degradation by DPP-IV and NEP.[8]

Liraglutide may have advantages over current therapies:

  • It acts in a glucose-dependent manner, meaning 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.[9]
  • It lowers blood triglyceride levels.


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 intramuscular injection is approximately half an 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 (less frequent than the currently approved Byetta form of exenatide, which is twice daily, but considerably more frequent than the once weekly Bydureon form of exenatide, which received marketing approval from the FDA on January 27, 2012).

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.[citation needed]

Thyroid cancer concerns[edit]

At exposures 8x greater than those used in humans, liraglutide caused a statistically significant increase in thyroid tumors in rats. In clinical trials, the rate of thyroid tumors in patients treated with liraglutide was 1.3 per 1000 patient years compared to 1.0 per 1000 patients in comparison groups. The Victoza label carries a boxed warning:

The FDA said 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.[11]

Pancreatitis concerns[edit]

In 2013, a study conducted at UCLA reported a "marked expansion" of the pancreas in eight organ donors who had been treated with incretin mimetic drugs such as Victoza and Byetta. In response, the United States FDA and the European Medicines Agency conducted a review of all available data regarding the possible connection between incretin mimetics and pancreatitis or pancreatic cancer. In a joint letter to the New England Journal of Medicine, the agencies concluded that "A pooled analysis of data from 14,611 patients with type 2 diabetes from 25 clinical trials in the sitagliptin database provided no compelling evidence of an increased risk of pancreatitis or pancreatic cancer" and "Both agencies agree that assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and in the media, are inconsistent with the current data. The FDA and the EMA have not reached a final conclusion at this time regarding such a causal relationship. Although the totality of the data that have been reviewed provides reassurance, pancreatitis will continue to be considered a risk associated with these drugs until more data are available; both agencies continue to investigate this safety signal."[12]


In 2010, Novo Nordisk breached the ABPI's code of conduct by failing to provide information about side effects of Victoza, and by promoting Victoza prior to being granted market authorization.[13]

In 2012, the non-profit consumer advocacy group Public Citizen petitioned the U.S. Food and Drug Administration (FDA) to immediately remove liraglutide from the market because they concluded that risks of thyroid cancer and pancreatitis outweigh any documented benefits.[14]

See also[edit]

exenatide (Byetta)


  1. ^ May 2008
  2. ^ "Clinical Study Shows Liraglutide Reduced Blood Sugar, Weight, And Blood Pressure In Patients With Type 2 Diabetes" June 2008
  3. ^
  4. ^ Oct 2008 Inc results of LEAD 6 extension
  5. ^ January 2009
  6. ^ Hirschler, Ben (January 13, 2010). "UPDATE 1-Novo starts tests on pill version of Victoza drug". Reuters. 
  7. ^ Sept 2008
  8. ^ (
  9. ^ "Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes" Diabetes Care. Oct 2008
  10. ^ Victoza Package Insert Date of Issue: January 2010 Version: 1
  11. ^ N Engl J Med, 362:774
  12. ^ "Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment — NEJM". 
  13. ^ "Novo Nordisk Limited, Eli Lilly and Company Limited, Grünenthal Ltd and Napp Pharmaceuticals Limited named in advertisements". Prescription Medicines Code of Practice Authority (PMCPA). Retrieved 2011-02-07. 
  14. ^ "Public Citizen to FDA: Pull Diabetes Drug Victoza From Market Immediately". Public Citizen. Retrieved 2013-04-02.