Liraglutide was approved for medical use in the European Union in 2009,[4] and in the United States in 2010.[11] It is available as ageneric medication.[12][13] In 2023, it was the 209th most commonly prescribed medication in the United States, with more than 2million prescriptions.[14][15]
Liraglutide is ananti-diabetic medication used for the treatment oftype2 diabetes orobesity.[6] Liraglutide (Victoza) isindicated as an adjunct to diet and exercise to improve glycemic control in people aged ten years of age and older with type 2 diabetes;[2] and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.[2] Liraglutide (Saxenda) is indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in people aged twelve years of age and older with body weight greater than 60 kilograms (130 lb) and obesity;[3] and in adults with overweight in the presence of at least one weight-related comorbid condition.[3]
Liraglutide may also be used together withdiet andexercise for chronic weight management in adults.[6] Liraglutide led to greater weight loss than some previous glucagon-like peptide analogues,[10] but is less effective than the standard weight loss dose ofsemaglutide.[21][22]
Aboxed warning in the USprescribing information cautions thatmedullary thyroid cancers have been observed in rats treated with liraglutide, but it is "unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans, as relevance to humans of such tumors in rodents has not been determined."[6]
At exposures eight times greater than those used in humans, liraglutide caused a statistically significant increase in thyroid tumors inrats. The clinical relevance of these findings is unknown.[2] In clinical trials, the rate of thyroid tumors in participants treated with liraglutide was 1.3 per 1000 participant years (4 people) compared to 1.0 per 1000 participants (1 person) in comparison groups. The sole participant in the comparator group and four of the five participants in the liraglutide group had serum markers (elevated calcitonin) suggestive of pre-existing disease at baseline.[2]
The USFood and Drug Administration (FDA) saidserumcalcitonin, abiomarker of medullary 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.[23]
In 2013, a group atJohns Hopkins University reported an apparently statistically significant association between hospitalization for acutepancreatitis and prior treatment with GLP-1 derivatives (such as exenatide) and DPP-4 inhibitors (such as sitagliptin).[24] 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 2014 letter, the agencies concluded that "A pooled analysis of data from 14,611 patients with type2 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 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."[25]
It reduces meal-relatedhyperglycemia (for 24 hours after administration) by increasinginsulin secretion (only) when required by increasing glucose levels, delaying gastric emptying, and suppressing prandialglucagon secretion.[26][27]
Liraglutide leads toinsulin release inpancreaticbeta cells in the presence of elevated bloodglucose. This insulin secretion subsides as glucose concentrations decrease and approach euglycemia (normal blood glucose level). It also decreasesglucagon secretion in a glucose-dependent manner and delaysgastric emptying. Unlikeendogenous GLP-1, liraglutide is stable againstmetabolic degradation bypeptidases, with aplasma half-life of 13 hours.[28][26]
Endogenous GLP-1 has aplasmahalf-life of 1.5–2 minutes due to degradation by the ubiquitousenzymes,dipeptidyl peptidase-4 (DPP4) andneutral endopeptidases (NEP). The half-life after intramuscular injection is approximately half an hour, so even administered this way, it has limited use as a therapeutic agent. The metabolically active forms of GLP-1 are theendogenous GLP-1-(7-36)NH2 and the more rare GLP-1-(7-37). The prolonged action of liraglutide is achieved by attaching afatty acid molecule at one position of the GLP-1-(7-37) molecule, enabling it to both self-associate and bind toalbumin within thesubcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Albumin binding also results in slower degradation and reducedrenal elimination compared to that of GLP-1-(7-37).[26]
Liraglutide injection pen sold under the brand name Saxenda.
Liraglutide is marketed under the brand name Victoza in the US, UK, UAE, Kuwait, India, Iran, Canada, Europe, Japan and the Philippines. It has been launched in Germany, Italy, Denmark, the Netherlands, Sweden, Japan, Canada, the United States, France, Indonesia, Malaysia and Singapore. Liraglutide is also known to be marketed as Saxenda in Australia, Brazil, Canada, Germany, Indonesia, Iran, Ireland, Israel, Norway, Czech Republic, Poland,[29] Portugal,[30] South Korea, Switzerland, The United Kingdom and the US, and also as Enligria and Quinliro in Russia.[31]
Liraglutide was approved by the USFood and Drug Administration (FDA) in 2014,[32] and by theEuropean Medicines Agency (EMA) in 2015,[5] for adults with abody mass index (BMI) of 30 or greater (obesity) or a BMI of 27 or greater (overweight) who have at least one weight-related condition.[33][34] Liraglutide was approved by the FDA in 2019, for treatment of children ten years or older with type2 diabetes, making it the first non-insulin drug approved to treat type2 diabetes in children sincemetformin was approved in 2000.[35]
Novo Nordisk made deals with generic manufacturers to enter the United States market in 2024.[36][37] The FDA approved the first generic liraglutide in December 2024, and granted the approval to Hikma Pharmaceuticals USA[12]
In 2010, Novo Nordisk breached theAssociation of the British Pharmaceutical Industry's (ABPI) code of conduct by failing to provide information about side effects, and by promoting it prior to being granted market authorization.[38]
In 2017, Novo Nordisk agreed to pay $58.65million to settle multiple whistleblower lawsuits alleging that the company had illegally marketed, promoted, and sold Victoza foroff-label uses (such as for type1 diabetes) in violation of theFederal Food, Drug, and Cosmetic Act and theFalse Claims Act.[40] Novo Nordisk paid an additional $1.45million to the states of California and Illinois to settle whistleblower cases alleging fraud against private commercial health insurers.[41]
In September 2024, it was reported that a study found that liraglutide helped children aged 6 to 12 years of age reduce their body mass index by 7.4% in a 56-week trial.[46]
^O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, et al. (August 2018). "Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial".Lancet.392 (10148). London, England:637–649.doi:10.1016/S0140-6736(18)31773-2.PMID30122305.S2CID52041320.
^Parks M, Rosebraugh C (March 2010). "Weighing risks and benefits of liraglutide--the FDA's review of a new antidiabetic therapy".The New England Journal of Medicine.362 (9):774–777.doi:10.1056/NEJMp1001578.PMID20164475.
^Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB (April 2013). "Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study".JAMA Internal Medicine.173 (7):534–539.doi:10.1001/jamainternmed.2013.2720.PMID23440284.S2CID425632.
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