'Game-changing' weight-loss jabs linked to ‘severe’ stomach problems, study says

Using weight-loss jabs such as Ozempic or Wegovy could increase the risk of “severe gastrointestinal problems”, a study has suggested.

The jabs, which have been hailed as a “game-changer” in the fight against obesity, were found to heighten the probability of pancreatitis, bowel obstructions and “stomach paralysis” in non-diabetics.

Researchers said that while it was “rare”, they warned hundreds of thousands of people could still be at risk around the world due to the drugs’ rising popularity.

A team from the University of British Columbia in Canada looked at health insurance claim records for about 16 million US patients, honing in on those who had been prescribed semaglutide or liraglutide between 2006 and 2020.

They included obese patients and excluded those with diabetes or who were on other anti-diabetic drugs.

Semaglutide and liraglutide are sold under the brand names Wegovy, Ozempic, Rybelsus and Saxenda and are manufactured by Novo Nordisk.

Known as GLP-1 agonists, they help increase the production of insulin and were originally developed for managing type 2 diabetes.

The team said previous research had highlighted the risk of gastrointestinal issues in patients with diabetes, but theirs is the first large, population-level study to explore the likelihood of it happening in non-diabetic people.

They analysed the records to see how many patients developed one of four gastrointestinal issues and compared them with those using another weight loss drug, bupropion-naltrexone.

They found those using weight loss jabs were 9.09 times more likely to suffer inflammation of the pancreas, which can, in some cases require surgery.

They were also 4.22 times more likely to develop a bowel obstruction and were at a 3.67 higher risk of gastroparesis, or “stomach paralysis”, which limits the passage of food from the stomach to the small intestine.

First author Mohit Sodhi, a graduate of UBC’s experimental medicine programme and fourth-year UBC medical student, said: “Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss.

“The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity or just general weight loss.

“People who are otherwise healthy may be less willing to accept these potentially serious adverse events.”

Dr Simon Cork, senior lecturer in physiology at Anglia Ruskin University, said the number of patients in the cohort taking the two drugs was “relatively low” due to them “not being licensed for the treatment of obesity for very long”.

However, despite this, he said the data is “reliable and of high quality”.

“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” Dr Cork added.

“It is vital that regulation is tightened to ensure that these drugs are only prescribed under the right circumstances.

“Whilst the likelihood of developing these conditions is still rare, when scaled up to the numbers who could potentially be prescribed these drugs we could start to see many people experiencing adverse effects from their use.”

Dr Cork said the benefits of taking the drugs to lose weight could outweigh the risks, due to the problems that can be caused by obesity.

The findings of the UBC study have been published in the Journal of the American Medical Association (Jama) and researchers now hope regulatory agencies and drugmakers will consider updating warning labels on their products.

Novo Nordisk, which makes semaglutide and liraglutide, was not involved in the analysis and did not have any approved GLP-1 products in 2006, which is the earliest point in the dataset.

A spokesman for the company said: “Patient safety is paramount to Novo Nordisk and we work closely with the UK authorities to continuously monitor the safety profile of our medicines.

“GLP-1 Ras have been used to treat type 2 diabetes for more than 15 years, and for treatment of obesity for eight years, including Novo Nordisk medicines that have been on the market for more than 10 years.

“Semaglutide has been examined in large global clinical development programs, and real world evidence studies and has cumulatively over 12 million patient years of exposure.

“Gastrointestinal (GI) events are well-known side effects of the GLP-1 class. For semaglutide, most GI side effects were mild to moderate in severity and of short duration.

"The gastrointestinal events led to permanent treatment discontinuation in 4.3% of patients. GLP-1s are known to cause a delay in gastric emptying, as noted in the label. Delayed gastric emptying, nausea and vomiting are listed as side effects within the SMPC.

“We recommend patients take these medications for their approved indications and under the supervision of a healthcare professional.

“Treatment decisions should be made together with a healthcare provider who can evaluate the appropriateness of using a GLP-1 based on assessment of a patient’s individual medical profile.

“We are continuously monitoring the safety profile of our products and collaborate closely with authorities to ensure patient safety, including adequate information on gastrointestinal side effects in the label.”

Want a quick and expert briefing on the biggest news stories? Listen to our latest podcasts to find out What You Need To Know.

The UBC study comes after Maccabi Health Services found semaglutide can “significantly” improve blood sugar control and weight loss in diabetics for up to three years.

Researchers said the effectiveness of a once-weekly dose of semaglutide to treat type 2 diabetes has been “demonstrated in randomised controlled trials”, but long-term data has “been lacking”.

The study, presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Hamburg and funded by Novo Nordisk, retrospectively analysed the data of 23,442 people.

Those included had used at least one prescription for semaglutide jabs between August 2019 and December 2022 and had one blood sugar control measurement (HbA1c) 12 months before and six months after starting treatment.

Before being prescribed semaglutide, 30% of patients were treated with insulin and 31% were treated with another drug from the weight-loss jab family, known as glucagon-like peptide-1 receptor agonists (GLP-1 RA).

Six months after starting on semaglutide, patients lowered their HbA1c by an average of 0.77% (from 7.6% to 6.8%) and reduced their body weight by an average of 4.7 kg (from 94.1 kg to 89.7 kg).

The National Institute for Health and Care Excellence (Nice) recommends the use of Ozempic to manage type 2 diabetes in England.

It also approved the use of Wegovy to aid weight loss on the NHS in England earlier this year, with its guidance recommending it should be used for a maximum of two years.

The drug launched in the UK last month and can be prescribed to people with a BMI of more than 30, or 27 in the presence of other co-morbidities, via specialist NHS services.

About 50,000 eligible patients are expected to benefit.

In June, the government launched a £40 million pilot to expand the use of weight-loss jabs in a bid to tackle the obesity crisis.

Prime Minister Rishi Sunak said using the latest drugs to support people in losing weight “will be a game-changer”.

In August, Novo Nordisk published the findings of its own five-year study on Wegovy, known as the Select trial.

It found use of the drug can slash the risk of a heart attack or stroke in obese people by a fifth.

The study included 17,604 adults over the age of 45 from across 41 countries, each with a BMI of more than 27 and established cardiovascular disease, with no history of diabetes.

Novo Nordisk has been approached for comment.