Liraglutide: What It Is and How the GLP-1 Agonist Works

At a glance

What is liraglutide?

Liraglutide is a GLP-1 receptor agonist, a peptide that closely mimics the natural gut hormone GLP-1. It shares about 97% of its structure with human GLP-1 and has a fatty-acid chain added so it binds to proteins in the blood and lasts long enough to be dosed once a day. It is made by Novo Nordisk and sold under two brand names, Victoza for type 2 diabetes and Saxenda for weight management, and a generic version is now available. Both branded forms are once-daily subcutaneous injections.

The history of liraglutide

Liraglutide's history includes three U.S. milestones:

Victoza improved on the earlier exenatide, which had to be injected twice a day. Its key engineering step, attaching a fatty-acid chain so the peptide clings to albumin and survives longer in the body, is the same approach Novo Nordisk later used to create once-weekly semaglutide. In that sense, liraglutide paved the way for the current generation of GLP-1 medicines, including semaglutide and tirzepatide.

How does it work?

Liraglutide activates the GLP-1 receptor, mimicking a natural gut hormone the body releases after eating. Through that receptor it prompts the pancreas to release insulin when blood sugar is high. Because this effect is glucose-dependent, meaning it works mainly when blood sugar is already elevated, liraglutide on its own carries a low risk of causing hypoglycemia. It also reduces the release of glucagon (a hormone that raises blood sugar) and slows the rate at which the stomach empties, which blunts the rise in blood sugar after a meal and helps a person feel full for longer. Beyond the gut and pancreas, liraglutide acts on appetite centers in the brain, where it increases feelings of fullness and reduces hunger and how much a person eats. This appetite effect is a large part of why it produces weight loss, not just better blood sugar control. Native GLP-1 breaks down within minutes, so liraglutide is engineered with a fatty-acid chain that binds to albumin in the blood. This extends its half-life to about 13 hours and allows once-daily dosing. In the SCALE weight-management trial, adults on the 3.0 mg dose lost about 8% of their body weight over 56 weeks, compared with about 2.6% on placebo.

Is it FDA-approved?

Yes. Victoza was first approved in 2010 for type 2 diabetes, and later to reduce cardiovascular risk in people with type 2 diabetes and heart disease. Saxenda was approved in 2014 for weight management, and both have since been approved for use in adolescents.

What is liraglutide prescribed for?

For type 2 diabetes, Victoza is prescribed to improve blood sugar control alongside diet and exercise. For weight management, Saxenda is approved for adults with obesity (a BMI of 30 or higher) or overweight (a BMI of 27 or higher) plus a weight-related condition such as high blood pressure or high cholesterol, and for adolescents aged 12 and older with obesity. It should not be used by people with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, or by anyone with a known allergy to liraglutide.

What are the side effects?

The most common side effects are gastrointestinal, and they are usually strongest when the dose is increased:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Decreased appetite
• Headache
• Fatigue Less common but more serious risks include:
• Thyroid C-cell tumors: liraglutide carries a boxed warning based on rodent studies. It is not known whether this happens in humans.
• Pancreatitis, or inflammation of the pancreas
• Gallbladder problems, including gallstones
• Acute kidney injury, usually from dehydration caused by vomiting or diarrhea
• Low blood sugar, especially when combined with insulin or a sulfonylurea
• Increased heart rate

Evidence strength

FDA approved: It is approved by the FDA for type 2 diabetes, chronic weight management, and cardiovascular risk reduction in type 2 diabetes, backed by the large LEAD, SCALE, and LEADER randomized controlled trial programs.

Sources: FDA prescribing information for Victoza and Saxenda (liraglutide); the SCALE weight-management trial (Pi-Sunyer et al., 2015, DOI: 10.1056/NEJMoa1411892) and the LEADER cardiovascular outcomes trial (Marso et al., 2016, DOI: 10.1056/NEJMoa1603827) in the New England Journal of Medicine, both indexed on PubMed; and a review of the history of GLP-1 receptor agonists. This document is educational and does not constitute medical advice.