Is Saxenda an appetite suppressant?

pharmaceutical-technology.com - Saxenda: profiling the first NHS weight loss drug for a decade

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Novo Nordisk’s Saxenda is the first medication to be endorsed for weight management in nearly a decade. Credit: Shutterstock. On 30th October, a new weight loss drug, Saxenda, became available on the NHS in England. Indicated for adult patients with obesity and additional risk factors, this is the first medication to be endorsed for weight management in nearly a decade. Also known as liraglutide 3mg, the drug is manufactured by Novo Nordisk and received its European marketing authorisation in 2015, before being launched in the UK two years later. Since then, it has been available privately – in June 2020, the high street pharmacy LloydsPharmacy started offering the drug as part of a weight loss programme. However, the NICE recommendation greatly increases the number of patients who will benefit. Pinder Sahota, corporate vice president and general manager at Novo Nordisk UK, said: “We are delighted that NICE has recommended Saxenda for the treatment of obesity on the NHS. This is testament to the value that this treatment offers, particularly during these challenging times, when policymakers and clinicians are highly focused on finding effective ways to address the prevalence of obesity across the UK.”

Why the NHS has taken this step

Up until recently, patients living with obesity in the UK had fairly limited options. Obesity is often still considered a lifestyle choice, rather than a medical condition, and interventions tend to focus on the value of diet and exercise to the exclusion of medical treatments. Since 2009, eligible patients have been able to buy a weight loss drug, Orlistat, over the counter. This drug works by interfering with the way fat is digested, and has helped many people lose weight. However, it is known for its unappealing side effects, including oily stools and diarrhoea. Bariatric surgery – available for very obese patients who haven’t responded to lifestyle changes and medicines – is generally effective, but carries serious health risks of its own. There is an obvious need for new treatments. Over the past 20 years, the number of people living with obesity in England has almost doubled – a problem that has been highlighted, tragically, during the Covid-19 pandemic. Public Health England has estimated that a body mass index (BMI) over 35 could increase a person’s risk of dying from Covid-19 by 40%, and that a BMI over 40 could increase the risk by 90%. In July, the government unveiled its new obesity strategy following the Covid-19 ‘wake-up call’. The plan includes limiting the food advertising children are likely to see, mandatory calorie labelling at restaurants and expanding weight management services on the NHS. Saxenda’s lauch, while not directly related to this obesity strategy, comes at a time when obesity-related health issues are top of mind. “Covid-19 helped focus politicians’ attention on the fact that obesity is a disease,” says Professor Carel Le Roux, consultant in metabolic medicine at Imperial College London. “Some people will be very successful with diet and they should continue with that, but those who don’t respond are not morally inferior – they’re just not biologically responding and we need to use medications and even surgical treatments.”

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He adds that the drug’s initial launch in the UK was based upon the one-year health data from clinical trials. However, the one-year data did not give insight into the health economics of the drug – for that, we had to wait for the three-year data. “The three-year data showed an 80% reduction in the risk of developing type 2 diabetes, and it’s that risk change, not the weight loss, that drives the health economics model,” he explains. “That’s why there was a delay in between the drug being launched and NICE approving it – NICE just didn’t have the data available to them to make a decision one way or the other.”

How Saxenda works

Saxenda is an injectable, once-daily medication that works by suppressing appetite. It is 97% similar to glucagon-like peptide-1 (GLP-1), a hormone released in response to food intake to create feelings of fullness and satiety. “We all make this hormone naturally, but if you have the disease of obesity you don’t make enough of it,” explains Le Roux. “What Novo Nordisk has done is they’ve purified the hormone and changed one amino acid, so instead of having a half life of two minutes it has a half life of 13.5 hours. If you take the peptide, you’d expect it to boost your natural level of GLP-1 and bind in exactly the same place the normal hormone would bind.” The protein binds to receptors in the pancreas, instructing the body to make insulin at the right time and in the right quantities. It binds to receptors in the part of the brain that controls hunger, ensuring that people with obesity suddenly feel more satisfied. It also helps regulate blood pressure and lessen inflammation. “When you put all those things together, the person with obesity feels less hungry and is prevented from getting type 2 diabetes,” says Le Roux. “You reduce the complications of obesity and other diseases.” Because this is a natural peptide, it needs to be administered subcutaneously to avoid being broken down by the stomach acid. However, the device is straightforward to use, and most of the potential side effects are gastrointestinal and transient. It will be utilised within specialist NHS weight management services, alongside lifestyle-based interventions.

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The drug will be available for those with a BMI of 35 or over (or 32.5 and over in the case of certain minority ethnic groups). To be eligible for NHS treatment, patients must also have pre-diabetes and a high risk of cardiovascular disease, based on risk factors like high blood pressure and cholesterol. “It will be available not as a weight loss drug but a health gain drug,” explains Le Roux. “The health gain NICE would like see is a reduction in the risk of people developing type 2 diabetes, while reducing their cardiovascular risk and improving their quality of life at the same time. We’re going to be responsible in prescribing it. We’re not going to tell patients that it’s going to make them thin and happy, because that’s not true – we’re going to tell patients it’ll make them healthier and more functional.” In clinical trials, people treated with Saxenda lost more weight than the placebo group, and were less likely to have been diagnosed with type 2 diabetes (3% compared to 11% in the control group). While not everybody responds to the medication, those who do respond tend to lose a significant proportion of their body weight. “Patients have a one in three in chance of responding biologically to this medication,” says Le Roux. “If we look at the people who do respond – i.e., those who are able to achieve 5% weight loss within 12 weeks – they go on to double digit weight loss. If we delve a little deeper, one in three people will lose more than 10% of their weight, or about two stone, and one in seven will lose 15% of their weight, or about three stone. That really makes a difference.” He hopes that this will be a step away from the ‘eat less move more’ model of obesity treatment, and more towards a considered approach that treats obesity as a disease. “Thirty years ago, if you had depression people would be telling you to cheer up, but now we treat depression as a chronic disease and we don’t discriminate against people on that basis,” he points out. “That’s a good example of how we’ve done well before, and we now need to do the same for obesity.”

pharmaceutical-technology.com - Saxenda: profiling the first NHS weight loss drug for a decade

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