Fourteen years ago, the older drug cousin of semaglutide (Ozempic and Wegovy) came onto the market. The drug, liraglutide, is sold under the brand names Victoza and Saxenda.
Author
Sebastian Furness
ARC Future Fellow, School of Biomedical Sciences, The University of Queensland
Patents for Victoza and Saxenda have now expried. So other drug companies are working to develop "generic" versions. These are likely be a fraction of current cost, which is around A$400 a month.
So how does liraglutide compare with semaglutide?
How do these drugs work?
Liraglutide was not originally developed as a weight-loss treatment. Like semaglutide (Ozempic), it originally treated type 2 diabetes.
The class of drugs liraglutide and semaglutide belong to are known as GLP-1 mimetics, meaning they mimic the natural hormone GLP-1. This hormone is released from your small intestines in response to food and acts in several ways to improve the way your body handles glucose (sugar).
How do they stop hunger?
Liraglutide acts in several regions of the unconscious part of your brain, specifically the hypothalamus, which controls metabolism, and parts of the brain stem responsible for communicating your body's nutrient status to the hypothalamus.
Its actions here appear to reduce hunger in two different ways. First, it helps you to feel full earlier, making smaller meals more satisfying. Second, it alters your "motivational salience" towards food, meaning it reduces the amount of food you seek out.
Liraglutide's original formulation, designed to treat type 2 diabetes, was marketed as Victoza. Its ability to cause weight loss was evident soon after it entered the market.
Shortly after, a stronger formulation, called Saxenda, was released, which was intended for weight loss in people with obesity.
How much weight can you lose with liraglutide?
People respond differently and will lose different amounts of weight. But here, we'll note the average weight loss users can expect. Some will lose more (sometimes much more), others will lose less, and a small proportion won't respond.
The first GLP-1 mimicking drug was exenatide (Bayetta). It's still available for treating type 2 diabetes, but there are currently no generics. Exenatide does provide some weight loss, but this is quite modest, typically around 3-5% of body weight.
For liraglutide, those using the drug to treat obesity will use the stronger one (Saxenda), which typically gives about 10% weight loss.
Semaglutide, with the stronger formulation called Wegovy, typically results in 15% weight loss.
The newest GLP-1 mimicking drug on the market, tirzepatide (Mounjaro for type 2 diabetes and Zepbound for weight loss), results in weight loss of around 25% of body weight.
What happens when you stop taking them?
Despite the effectiveness of these medications in helping with weight loss, they do not appear to change people's weight set-point.
So in many cases, when people stop taking them, they experience a rebound toward their original weight.
What is the dose and how often do you need to take it?
Liraglutide (Victoza) for type 2 diabetes is exactly the same drug as Saxenda for weight loss, but Saxenda is a higher dose.
Although the target for each formulation is the same (the GLP-1 receptor), for glucose control in type 2 diabetes, liraglutide has to (mainly) reach the pancreas.
But to achieve weight loss, it has to reach parts of the brain. This means crossing the blood-brain barrier - and not all of it makes it, meaning more has to be taken.
All the current formulations of GLP-1 mimicking drug are injectables. This won't change when liraglutide generics hit the market.
However, they differ in how frequently they need to be injected. Liraglutide is a once-daily injection, whereas semaglutide and tirzepatide are once-weekly. (That makes semaglutide and tirzepatide much more attractive, but we won't see semaglutide as a generic until 2033.)
What are the side effects?
Because all these medicines have the same target in the body, they mostly have the same side effects.
The most common are a range of gastrointestinal upsets including nausea, vomiting, bloating, constipation and diarrhoea. These occur, in part, because these medications slow the movement of food out of the stomach, but are generally managed by increasing the dose slowly.
Recent clinical data suggests the slowing in emptying of the stomach can be problematic for some people, and may increase the risk of of food entering the lungs during operations, so it is important to let your doctor know if you are taking any of these drugs.
Because these are injectables, they can also lead to injection-site reactions.
During clinical trials, there were some reports of thyroid disease and pancreatitis (inflammation of the pancreas). However, it is not clear that these can be attributed to GLP-1 mimicking drugs.
In animals, GLP-1 mimicking drugs drugs have been found to negatively alter the growth of the embryo. There is currently no controlled clinical trial data on their use during pregnancy, but based on animal data, these medicines should not be used during pregnancy.
Who can use them?
The GLP-1 mimicking drugs for weight loss (Wegovy, Saxenda, Zepbound/Mounjaro) are approved for use by people with obesity and are meant to only be used in conjunction with diet and exercise.
These drugs must be prescribed by a doctor and for obesity are not covered by the Pharmaceutical Benefits Scheme, which is one of the reasons why they are expensive. But in time, generic versions of liraglutide are likely to be more affordable.
Sebastian Furness receives funding from the National Health and Medical Research Council and Australian Research Council.
