Liraglutide
Liraglutide is a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist with a fatty acid side chain. It is FDA-approved for type 2 diabetes (Victoza) and chronic weight management (Saxenda).
Overview
Liraglutide is a synthetic analogue of human glucagon-like peptide-1, an incretin hormone secreted by the gut in response to food. Developed by Novo Nordisk, it was one of the first GLP-1 receptor agonists designed around the principle of albumin binding through a fatty acid chain, an approach later extended in semaglutide. The modification slows absorption and clearance, allowing once-daily injection in contrast to native GLP-1, which is degraded within minutes.
Liraglutide is FDA-approved as Victoza for glycemic control in type 2 diabetes and as Saxenda for chronic weight management. Its clinical development included the LEAD trials in type 2 diabetes, the SCALE trials in obesity and the LEADER cardiovascular outcomes trial. Because of its long track record, it is a common comparator and reference compound in incretin research and in studies of newer, longer-acting agents.
Compare: Semaglutide vs liraglutide.
Structure
Liraglutide is based on human GLP-1(7-37), a 31-residue peptide, and shares about 97% sequence identity with it. Lysine at position 34 is replaced with arginine, leaving a single lysine at position 26. That lysine carries a palmitic acid (C16) chain attached through a γ-glutamic acid spacer. The fatty acid promotes reversible binding to albumin and self-association at the injection site, slowing absorption and protecting the peptide from enzymatic degradation. Unlike semaglutide, liraglutide retains alanine at position 8.
Mechanism
Liraglutide is an agonist of the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the brain, the gastrointestinal tract and other tissues. It enhances glucose-dependent insulin secretion, suppresses inappropriate glucagon release and slows gastric emptying, which together lower blood glucose.
Effects on body weight are attributed mainly to actions in brain regions involved in appetite regulation, leading to reduced food intake. Albumin binding and slowed absorption give it a duration of action suited to once-daily dosing, shorter than once-weekly analogues such as semaglutide.
Research
Type 2 diabetes: the LEAD program
The LEAD phase 3 trials evaluated liraglutide in type 2 diabetes, alone and in combination with other glucose-lowering drugs, compared with placebo and active comparators. They showed improvements in HbA1c and modest weight reduction. These trials supported FDA approval of Victoza in 2010. Later trials compared liraglutide with other GLP-1 receptor agonists, and it became a standard comparator in the field.
Cardiovascular outcomes: LEADER
LEADER was a large randomized trial in people with type 2 diabetes at high cardiovascular risk, published in 2016. Liraglutide met its primary endpoint, reducing the rate of major adverse cardiovascular events compared with placebo. LEADER was among the first trials to show a cardiovascular outcome effect for a GLP-1 receptor agonist and led to an expanded indication for Victoza.
Obesity: the SCALE trials
The SCALE program evaluated liraglutide 3.0 mg in adults with obesity or overweight with related conditions. In the main trial, published in 2015, liraglutide combined with lifestyle intervention produced greater weight loss than placebo and met its primary endpoints. These results supported approval of Saxenda for chronic weight management, later extended to adolescents. Weight loss was smaller than that later reported for semaglutide and tirzepatide.
Other research
Liraglutide has been studied in type 1 diabetes, metabolic dysfunction-associated steatohepatitis, polycystic ovary syndrome and neurodegenerative disease, with variable results. Preclinical studies have explored effects on the brain, liver and cardiovascular system. Results outside approved indications are investigational, and labeling defines the approved uses. Liraglutide has also served as an active comparator in head-to-head trials of newer incretin agents, which makes its results a useful benchmark across the field.
Regulatory status
Liraglutide is FDA-approved as Victoza for type 2 diabetes, including reduction of cardiovascular risk in adults with established cardiovascular disease, and as Saxenda for chronic weight management. Indications and populations are defined by current labeling. It is also approved in many other countries. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A certificate of analysis for liraglutide should confirm identity by mass spectrometry, with the expected mass including the palmitoyl-γ-glutamyl side chain, and report reverse-phase HPLC purity. Key impurities include peptides lacking the side chain, side-chain isomers, deletion or insertion sequences, and oxidized tryptophan. Liraglutide self-associates and can form aggregates or fibrils, so size-exclusion chromatography is relevant. Pharmacopoeial and regulatory guidance for synthetic liraglutide, including comparison with recombinant-origin material, provides useful benchmarks. Counter-ion and net peptide content should be stated for research material.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized liraglutide sealed at -20 °C, protected from light and moisture, and allow vials to reach room temperature before opening. In solution, the fatty acid chain promotes self-association and adsorption to surfaces, and the peptide can aggregate when agitated or exposed to heat; gentle handling and low-binding containers help. Solutions for lab use should be refrigerated for short-term work, aliquoted for longer storage, and not subjected to repeated freeze-thaw cycles. Approved products have their own labeled storage conditions.
Download the Liraglutide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention Liraglutide in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
What is the difference between liraglutide and semaglutide?
Both are GLP-1 receptor agonists from Novo Nordisk that use a fatty acid chain for albumin binding. Liraglutide uses a C16 fatty acid and is given once daily. Semaglutide has an Aib substitution at position 8, a longer C18 diacid chain and a linker, giving a longer half-life that supports once-weekly dosing and an oral form.
Is liraglutide FDA approved?
Yes. Liraglutide is FDA-approved as Victoza for type 2 diabetes, including cardiovascular risk reduction in certain adults, and as Saxenda for chronic weight management. The specific indications and patient populations are set out in the current prescribing information for each product.
Is liraglutide a peptide?
Yes. Liraglutide is a 31-residue peptide based on human GLP-1, modified with an amino acid substitution and a palmitic acid chain attached through a glutamic acid spacer. Such fatty acid modifications are known as lipidation, a common strategy for extending the duration of peptide drugs.
Related compounds
- Semaglutide
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy).
- Exenatide
Exenatide is a 39-amino-acid GLP-1 receptor agonist, a synthetic version of exendin-4 found in Gila monster saliva. It was the first GLP-1 receptor agonist approved by the FDA, as Byetta and later Bydureon, for type 2 diabetes.
- Tirzepatide
Tirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors. It is FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound).
- Pramlintide
Pramlintide is a synthetic analogue of the pancreatic hormone amylin, modified with three proline substitutions to prevent aggregation. It is FDA-approved as Symlin for use with mealtime insulin in type 1 and type 2 diabetes.
References
- Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016. Find on PubMed
- Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015. Find on PubMed
- PubMed: all indexed literature on Liraglutide
- ClinicalTrials.gov: registered studies mentioning Liraglutide
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