Can weight loss drugs ‘solve’ obesity?
www.nesta.org.uk/blog/can-weight-loss-drugs-solve-obesity/
www.nesta.org.uk/blog/can-weight-loss-drugs-solve-obesity/
The new generation of weight loss medicines are an important treatment tool that could accelerate our mission to halve obesity, but they would fall very far short as the cornerstone of a national obesity strategy.
At Nesta, we have a clear mission – to help more people live a healthy life, for longer. Working with a range of partners, our goal is to halve obesity in the UK by 2030, helping at least 9 million people move to a healthy weight.
To achieve our goal, we need to target the root cause of obesity – our food environment. We know that rising rates of obesity are mainly due to the unhealthiness of the food that’s available, accessible and affordable in our society, rather than individual dietary choices or willpower.
Our aim is to improve the healthiness of the food we all eat. This is a long-term ambition that will take years of reform, regulation and coordination between manufacturers, retailers and health bodies.
In parallel, we need treatments to help people living with the health effects of obesity today. That’s where we think the new generation of weight loss medications, known as GLP-1 agonist medicines (GLP-1s), can help.
Read our overview and click the headings to find out more.
The technical name of these medicines is glucagon-like peptide-1 receptor agonists (GLP-1s). GLP-1s have been used for treating diabetes for years and have only recently been used for treating obesity alone. They are generally injected with a pen, but oral formulations are becoming available.
The medicines mimic a naturally occurring hormone to slow down the speed of digestion so people feel full more quickly and for longer. They can also reduce appetite. As a result, people are able to maintain calorie-restricted diets for long enough to achieve significant weight loss.
In the UK, these drugs are only available alongside an accompanying weight management programme.
Semaglutide and tirzepatide are currently the two most effective and talked-about GLP-1 medicines.
Semaglutide is sold under the brand name Ozempic for the management of diabetes, but sold as Wegovy when used for weight loss. Both are approved for use in the UK and recommended by NICE.
Tirzepatide is sold under the brand name Mounjaro for the management of diabetes and under the brand name Zepbound for weight loss.
Only Mounjaro is approved for use in the UK and recommended by NICE. A Zepbound appraisal expected in March 2024.
The early evidence shows that, when combined with diet, nutrition and lifestyle support, weight loss drugs can help people to achieve significant weight reductions. They can help people to lose weight quickly and consistently, reducing their likelihood of developing obesity-related health problems and preventing or delaying the onset of chronic conditions such as diabetes.
Until recently, medical options to aid weight loss have been limited, with few treatment options consistently achieving clinically significant weight loss.
At present in the UK, there are four categories of weight loss intervention:
The evidence shows that most people struggle to achieve and maintain their required weight loss with non-surgical interventions.
Bariatric surgery is considered a last resort but is very effective, with patients achieving around 25-30% weight loss after 1-2 years.
However, surgery is expensive, not uniformly available and carries the risks inherent with a major operation.
Ideally, any weight loss intervention would be long term – and until now bariatric surgery has been the only really effective solution on this measure.
Over 1 million people in England would qualify for bariatric surgery but we carry out only 6-7,000 operations each year.
Although two thirds of these procedures are on the NHS, overall pressures mean its capacity to provide this surgery is limited.
There is a greater need and demand for treatments for obesity than we are able to meet
A bar chart showing the demand for obesity treatment versus the people receiving it.
Over 1 million people in England would qualify for bariatric surgery.
Only 35,000 people access Tier 3 weight management services.
Only 7000 receive bariatric surgery.
Likewise there are similar constraints on weight management services (specialist interventions that focus on psychological support, nutrition, lifestyle and exercise). These are currently limited at around 35,000 places per year and are not uniformly available across the UK.
There are a number of trials evaluating the efficacy and safety of GLP-1 medications, with more research underway.
The Semaglutide Treatment Effect in People with Obesity (STEP) Phase 1 study found that participants lost an average of 14.9% of their body weight over the trial period of 68 weeks.
The SURMOUNT–1 Phase 1 study found tirzepatide even more effective, with an average 16-22% weight reduction at 72 weeks (depending on dosage).
As with many medicines, the drugs don’t work as effectively for everyone, though it's not yet well understood why.
The new weight loss medicines are significantly more effective than any pharmacological or lifestyle option previously available, leading to an average weight loss of around 15-20% of body weight – comparable with bariatric surgery.
Researchers are currently investigating the extent to which overall health improves when people lose weight with GLP-1s. Benefits shown to date include improved heart health, with fewer cardiovascular events, decreased chronic muscular-skeletal pain and improvements in diabetic or pre-diabetic factors.
Some patients have also reported that they help with other compulsive behaviours like nail biting and smoking, though further research is underway.
Early evidence indicates that people hit a weight loss plateau after around one year, and only keep weight off as long as they are receiving treatment (which is currently only approved and funded for a treatment period of two years). A year after they stop, participants typically put two-thirds of the weight back on.
In its submission to NICE, manufacturer NovoNordisk assumes that three years after patients finish treatment, there will be no weight difference between those who have been on semaglutide and those who received only lifestyle interventions.
However, the evidence so far shows that the weight loss doesn’t last. Current indications are that patients regain weight after their treatment period ends, so while the medicines are effective, at present, bariatric surgery remains the most effective treatment in the very long term.
The reported side effects of GLP-1s include nausea, vomiting, diarrhoea and constipation.
While evidence is limited, some users have also reported losing interest in food in general or feeling so nauseous they don’t want to eat, and some develop an intolerance for certain types of food, such as foods high in fat.
The side effects have not resulted in significant drop-outs in trials but it's expected that they would have some impact on adherence more generally.
Though they can’t solve the problem of obesity in Britain alone, pharmacological treatments carry many advantages over surgery – they are reversible, carry less risk, are cheaper and could be easier and quicker to access.
Despite their limitations and side effects, it's possible to imagine that in time these treatments may become a long-term management option for some, in the same way as statins are used to manage cholesterol.
Since September, Wegovy (semaglutide) has been available on the NHS as a weight loss treatment. It’s available for a maximum period of up to two years – but only for people referred to a specialist weight management programme that also includes a reduced calorie diet and increased physical activity.
To qualify for the treatment patients should have a BMI of at least 35 and a weight-related health condition such as hypertension or cardiovascular disease. Some people with a BMI between 30 - 34.9 may also be eligible if they meet the referral criteria for specialist weight management. People from certain ethnic minorities may also qualify under lower BMI criteria.
A two year pilot to expand specialist weight management services beyond hospital settings and make weight loss medicines available to more people is currently under development. It will look at whether GPs could prescribe these medicines and how support could be provided in the community and digitally.
Wegovy is not available on the NHS in Northern Ireland, as it does not have Tier 3 weight management services at present.
GLP-1s would likely save the NHS money in the long run, because of the costs that are otherwise incurred on obesity-related admissions, thought to be £6.5 billion annually (including diabetes care).
However, we estimate that it would cost £16.5 billion a year to halve adult obesity in England by 2030 using GLP-1s – almost equivalent to the entire annual NHS prescribing budget.
The drugs alone would cost £9.3 billion every year, with the rest made up of the required wraparound support.
That's an additional cost and activity level that an already stretched NHS could not absorb, with potential savings still an assumption at this point in time.
Whilst the treatments are considered cost-effective by NICE, availability and access to NHS weight management services (through which these treatments are available) remains patchy.
Though there are plans to explore the delivery of weight management through GP and community/online settings, without additional investment the ability of these services to absorb the increased demand and activity caused by GLP-1s will be limited.
Wegovy can be bought privately, but it requires an assessment, a prescription and specialist weight management support. It is not available over the counter and private supplies are limited.
It can be accessed through weight loss treatment programmes from some major high street pharmacies, as well as through a number of weight loss management companies that have begun to supply Wegovy as an optional part of their offer (including Nesta investment Habitual, a weight loss programme that combines a meal programme and behavioural support).
Depending on the dosage, a month’s supply is approximately £200 - £300 privately.
Supply constraints for semaglutide have been widely reported, resulting in NovoNordisk’s letter to health professionals in August 2023. Production constraints are anticipated to resolve by mid-2024.
Although some people will be able to pay for the medicines privately, most of those who would benefit the most from weight loss could not afford to do so – the NHS is their only option.
Therefore the private cost and the constrained capacity of NHS weight management services could exacerbate health inequalities in the short term, with the wealthiest able to access the treatments and the poorest not.
By creating a preventative food environment, not only would we reduce the share of the population who are overweight or living with obesity – we would also reduce the treatment bill in future.
A healthy food environment would increase treatment effectiveness by reducing the dietary factors that could hamper weight-loss. In turn this could actually improve the results from GLP-1s and other interventions.
More accessible and affordable healthy food will make it easier to lose weight during treatment and maintain weight loss post-treatment.
It's clear there could be a positive feedback loop between treatment and prevention.
We are already seeing early indications from the United States that users of these treatments are making different food choices. As an early sign of what might be to come here in the UK, Nestle recently announced new formulations of foods for people taking semaglutide.
The magnitude of the obesity challenge means we should welcome new treatment options. Prevention and treatment needn’t be put forward as an ‘either/or’; they work together. But we must ensure that an exciting treatment option doesn’t crowd out the hard and essential work of prevention.
GLP-1s are not a miracle cure – they do not directly cause weight loss, but by limiting appetite they make it easier for people to adhere to restricted diets. In effect, they supercharge more traditional calorie-restriction interventions.
But if we consider obesity a chronic condition, they can be a necessary and life-saving treatment for its management – avoiding radical surgery, delaying complications, improving quality of life, and extending lifespans.
At a system level, they are a promising tool at a time when health services have struggled to keep pace with the level of need.
But these medicines should be understood as an aspect of a wider obesity strategy, not a replacement for it.
Without targeting the causes of rising obesity trends, treatment costs could quickly become unsustainable and provision inequitable, with undesirable societal consequences.
How to think about GLP-1s as part of a population-wide obesity strategy
A indicative graph with three trend lines over time: obesity, change in food environment and people on GLP-1s.
The line of obesity is declining linearly over time, the line of change in food environment is increasing linearly over time - they intersect at a later point in time before diverging again.
The line of people of GLP-1s is lower than the obesity line. It declines over time irregularly but smoothly, intersecting with the change in food environment line at earlier point than the change in food environment line intersects with the obesity line.
Treatment alone will not solve the long term issues in our food environment that cause obesity.
Weight loss drugs are useful for helping people living with obesity today but ultimately we need to reduce the number of people seeking help for excess weight in the first place.
Over time, it’s crucial that we reduce the demand for medical obesity treatments (and their associated costs) by improving the healthiness of the foods we are being sold.
GLP-1s hold huge potential for accelerating our progress to halving obesity and improving population health, but they will only be truly transformative alongside sustained efforts to address obesogenic food environments and a focus on preventing obesity in future.
