Could weight loss drugs help to avert a national obesity crisis?

Today, the government announced a two-year pilot backed by £40 million of funding which will explore how weight loss drugs could help to tackle the obesity crisis.¹

Rates of overweight and obesity in England have tripled since 1975, and now just under two-thirds of the population are overweight or obese.²

Obesity is one of the leading causes of severe health conditions such as cardiovascular disease, diabetes and cancer, and it costs the NHS £6.5 billion a year. In 2019/20, there were more than one million admissions to NHS hospitals where obesity was a factor.¹

The government hopes trialling new drugs, such as semaglutide (Wegovy), in clinical settings will help to cut waiting lists by reducing the number of people who have weight-related illnesses, as this group tends to need more support from the NHS and could end up needing operations linked to their weight.

However, weight loss drugs do not come without controversy, and experts are concerned that the benefits of drugs like semaglutide may not be all they seem.

People on semaglutide lost 15kg in a clinical trial

NICE approved semaglutide in March of this year. The weight loss injection suppresses appetite by mimicking the hormone glucagon-like peptide-1 (GLP-1), creating a feeling of fullness.

The drug has historically been used to help control blood sugar in people with type 2 diabetes, until a large clinical trial showed that a 2.4mg dose of the drug (alongside reduced-calorie diet and exercise regime) caused participants without diabetes to lose, on average, 15.3kg over 68 weeks. The placebo group lost just 2.6kg.³

Further reading:

• Controversial weight loss drug semaglutide approved for NHS use
• Weight loss jab to be made available from UK pharmacies
• DNP and diet pills: the dangers of unregulated weight loss medication

The Prime Minister, Rishi Sunak, says weight loss drugs like semaglutide will be a “game-changer” for tackling the obesity crisis and reducing NHS waiting times.

However, due to strict NICE guidance, the new treatment will only be available to around 35,000 people.

Wider access to weight loss drugs could ‘further entrench eating disorders’

NICE advises that semaglutide should only be prescribed for a maximum of two years within a specialist weight management service, which significantly limits the amount of people who could be eligible for the treatment.⁴

This is, in part, to prevent people with a normal BMI from accessing the drug. Currently, the drug is only available to people who have at least one weight-related comorbidity and a BMI of at least 35kg/m² (i.e. those who are considered to be clinically obese).

However, an investigation by The Guardian found that online pharmacies have been prescribing semaglutide to people of a healthy weight. On two occasions an online consultation for semaglutide (Ozempic) – accurately filled in by a 5ft 7in female reporter weighing 57kg (9 stone), resulting in a BMI of about 20 – was immediately approved and dispatched by the online pharmacy Daily Chemist.⁵

Other online pharmacies were also found to have authorised prescriptions to individuals who deliberately submitted incorrect weight BMI information in order to get a prescription of the weight loss medication.⁵

Eating disorder charities have expressed concern that wider availability of the drug could therefore further entrench eating disorder thoughts and behaviours.”

Tom Quinn from the charity Beat told the BBC that Wegovy or other weight-loss medications “should only be sold under the strictest possible conditions, with stringent physical and mental health checks to ensure patients are well enough.”⁶

This is because these medications can be very attractive to people with eating disorders, and can make those affected “even more unwell”.

“It is vital that people are aware of the dangers of abusing medication in order to lose weight and there should be more education on their effects,” he said

People who stopped using Wegovy regained their original weight in five years

There is also concern that the weight loss drug will not provide a long-term solution to the UK’s obesity epidemic, after Novo Nordisk, Wegovy’s manufacturer, admitted that patient who stop using the weight loss drug risk regaining their original body weight within the space of five years.⁷

Novo Nordisk added that within two to three years, patients could gain back around half of their original body weight if they stop using the treatment. And although this weight gain is slower than previously predicted (early studies showed patients could regain two-thirds of their lost weight one year after discontinuing the use of the drug), this data indicates that continuous treatment would be required to maintain weight and health improvement.⁷

NICE says the two-year maximum treatment plans mirrors the clinical and financial modelling seen in specialist weight management services, where patients only “very exceptionally” stay in weight management services beyond two years.⁸

Despite an NHS England representative suggesting that the psychological impact of stopping semaglutide treatment after two years at the same time as being discharged from specialist weight management services could be “detrimental”, NICE concluded the NHS would not be able to offer the treatment for any longer “given the marketing authorisation and clinical evidence base”.⁸

Indeed, there is currently no data on the effects of taking semaglutide for longer than two years. However, NICE says that when further evidence become available, “it might be possible to consider long-term use in other settings if the evidence suggests that long-term or lifetime use is clinically and cost effective.”⁸

Side effects of semaglutide

No unexpected safety issues of semaglutide have arisen to date, and one study concluded that given the beneficial metabolic and cardiovascular actions of semaglutide, and the low risk for severe adverse events, semaglutide has an overall favourable risk/benefit profile.⁹

However, the study did find that semaglutide may induce mostly mild-to-moderate and transient gastrointestinal disturbances (such as nausea, vomiting and diarrhoea) and increases the risk of gallstones (or cholelithiasis).⁹

There have also been reports that semaglutide may cause pancreatitis,¹⁰ but the study’s authors say definitive conclusions for pancreatic and thyroid cancer cannot be drawn at this point due to low incidence of these conditions.

The authors also note that due to its potent glucose-lowering effect, patients at risk for deterioration of existing diabetic retinopathy should be carefully monitored if treated with semaglutide, particularly if also treated with insulin.

According to Diabetes UK, other side effects may include:³

• Burping
• Dizziness
• Fatigue
• Hypoglycaemia (when used in combination with insulin or sulfonylureas).

Is Wegovy the only weight loss medication which has shown promise?

According to Reuters, the enormous demand for weight loss treatments like Wegovy could support as many as 10 competing products with annual sales reaching up to $100 billion within a decade.¹¹

Pfizer, Amgen and Altimmune are all working on similar weight-loss therapies, while five other drugs have already been approved by the US Food and Drug Administration (FDA), including Bupropion-naltrexone (Contrave), Liraglutide (Saxenda), Orlistat (Xenical, Alli), Phentermine-topiramate (Qsymia), and Setmelanotide (Imcivree).

Novo Nordisk are therefore likely to face significant competition from other weight loss drug manufacturers in the near future.

This comes following the suspension of Novo Nordisk as a member of the Association of the British Pharmaceutical Industry (ABPI) because of “serious breaches” of the organisation’s code of practice.¹²

Novo Nordisk was suspended for two years by the ABPI for failing to clearly disclose its sponsorship of a weight management training course for healthcare professionals on LinkedIn. The post included positive information on its obesity drug Saxenda (liraglutide).¹³ Saxenda was approved by NICE in 2021 for adults with obesity, but Wegovy is considered safer and more effective.¹⁴

The course was offered by a third-party training provider and Novo Nordisk said it had supported it “at arm’s length”, but the ABPI said it was concerned that Novo Nordisk did not recognise that this was a large scale Saxenda promotional campaign which the company had knowingly paid for and which was “disguised.”¹³

As a result, the company will not be able to access the wider benefits of ABPI membership. This includes the removal of Novo Nordisk from all ABPI groups, including the ABPI Board, and access to any ABPI information and briefing.

The PMCPA will undertake further audits of Novo Nordisk’s compliance in late 2023 and 2024, and these reports will need to show “clear, significant, and then sustained improvement to industry standards” in order for the ABPI Board to consider allowing Novo Nordisk to resume full engagement with the ABPI at the end of the two-year suspension.¹³

This is the eighth occasion in the past 40 years the ABPI board has issued such a significant sanction.¹³

Government pilot could “benefit some patients”

The suspension of Novo Nordisk led the Royal College of General Practitioners (RCGP) to cut ties with the company, and cancel a number of existing projects which they provided the funding for.¹⁴

Despite this, the RCGP says that the government scheme to provide greater access to obesity drugs in primary care is “worth exploring” and “may benefit some patients”, but it must be done “based on evidence of long-term benefit”.¹⁵

For some patients, “other interventions” may have to be used alongside semaglutide to ensure weight loss is sustained, notes Professor Kamila Hawthorne, Chair of the RCGP.

“Sufficient availability of the drug must be ensured ahead of any roll out, so as not to raise patients’ expectations, as there may be a significant number of people who would benefit from it.

“We look forward to [the pilot] being robustly evaluated, taking the above points into account, before it is rolled out more widely, and as strategies to tackle obesity are developed,” she concludes.

 

References

1. New drugs pilot to tackle obesity and cut NHS waiting lists. Department of Health and Social Care. 2023. Available at: https://www.gov.uk/government/news/new-drugs-pilot-to-tackle-obesity-and-cut-nhs-waiting-lists
2. Turning point: The case for new action in tackling obesity in England. Future Health. 2022. Available at: https://www.futurehealth-research.com/site/wp-content/uploads/2022/12/Turning-point-the-case-for-new-action-in-tackling-obesity-in-England-FINAL-1.pdf
3. Semaglutide: A Complete Guide. Diabetes.co.uk. 2022. Available at: https://www.diabetes.co.uk/diabetes-medication/semaglutide.html
4. NICE recommended weight-loss drug to be made available in specialist NHS services. NICE. 2023. Available at: https://www.nice.org.uk/news/article/nice-recommended-weight-loss-drug-to-be-made-available-in-specialist-nhs-services
5. Online UK pharmacies prescribing weight loss jabs to people with healthy BMI. The Guardian. 2023. Available at: https://www.theguardian.com/society/2023/may/10/online-uk-pharmacies-prescribing-weight-loss-jabs-to-people-with-healthy-bmi-investigation
6. Wegovy weight loss jab to be sold by UK chemist shops. BBC. 2023. Available at: https://www.bbc.co.uk/news/health-64623284
7. Novo Nordisk says stopping obesity drug may cause full weight regain in 5 years. Reuters. 2023. Available at: https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-stopping-obesity-drug-may-cause-full-weight-regain-5-years-2023-03-30/
8. Semaglutide for managing overweight and obesity. Technology appraisal guidance. NICE. 2023. Available at: https://www.nice.org.uk/guidance/ta875/resources/semaglutide-for-managing-overweight-and-obesity-pdf-82613674831813
9. Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021. 7;12:645563. doi: 3389/fendo.2021.645563.
10. I Took Ozempic, Then I Got Pancreatitis. Healthline. 2023. Available at: https://www.healthline.com/health-news/ozempic-side-effect-pancreatitis
11. Novo Nordisk rivals see room to compete in $100 billion weight-loss drug market. Reuters. 2023. Available at: https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-rivals-see-room-compete-100-bln-weight-loss-drug-market-2023-05-04/
12. Novo Nordisk is suspended from ABPI membership. ABPI. 2023. Available at: https://www.abpi.org.uk/media/news/2023/march/novo-nordisk-is-suspended-from-abpi-membership/
13. Wise J. Novo Nordisk suspended from industry body over serious breaches BMJ 2023; 380 :p634 Available at: https://www.bmj.com/content/380/bmj.p634
14. Wegovy® VS Saxenda®. Second Nature. 2023. Avaiable at: https://www.secondnature.io/guides/lifestyle/wegovy-vs-saxenda
15. RCGP statement on partnership with Novo Nordisk. RCGP. 2023. Available at: https://www.rcgp.org.uk/news/novo-nordisk