GLP-1 agonists for obesity are being rationed in the UK, but that hasn’t stopped doctors considering how patients should be treated in the long term.

Elisabeth Mahase reports

Injectable appetite suppressant drugs should be considered a lifelong treatment for obesity rather than a two year fix, researchers have argued.

At a briefing at London’s Science Media Centre on the GLP-1 “weight loss drugs” that have made headlines around the world in the past year, speakers said that the UK’s current prescribing limit of two years was based on economics rather than clinical benefit.

“With regards to the two year rule, it’s a cost measure rather than a clinical measure,” said Barbara McGowan, consultant endocrinologist and obesity physician at Guy’s and St Thomas’​ NHS Foundation Trust on 26 July. “We all agree that obesity is a chronic disease. We feel that these medications should not be stopped after two years. You wouldn’t stop a statin, you wouldn’t stop a blood pressure tablet.”

Regaining weight was also a concern when the treatment ended, along with the “psychological issues” that came with that, she added.

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injectable antidiabetes drugs that work by increasing the secretion of insulin and suppressing appetite. Two are approved on the NHS: liraglutide (marketed as Saxenda) and semaglutide (Wegovy), although semaglutide has yet to be officially launched, because of supply problems.

Guidelines on liraglutide from the National Institute for Health and Care Excellence (NICE) published in March acknowledged that limiting treatment to two years for a long term condition was “not ideal.” However, it “accepted that the cost-effectiveness estimate was based on a single course of treatment of no longer than two years” and that this was the length of time a person remained under NHS tier 3 weight management services (non-surgical services based in secondary care).

Carel le Roux, professor of metabolic medicine at Ulster University, said that although he believed that NICE “made the right decision at the time,” he hoped it would revise the limit as more data on long term effects were published and as costs fell. “Drugs become cheaper as time goes on, and liraglutide is coming off patent this year,” he said. “So we really hope, with more competition in the market, that the drug prices will come down. That will fundamentally change the health economic model.”

The Glasgow GP and former BMJ columnist Margaret McCartney has previously raised concerns over the approved duration of treatment and what happens when people are taken off the drugs but has also flagged the potential conflicts of interest of expert speakers being widely quoted in the media.

Public health focus

Speaking to The BMJ, McCartney said that decisions on whether the drugs could be used for an extended period relied on trials showing long term safety. She added that a patient register was needed to track long term effects. “We don’t know if there are substantive side effects. NICE should not be making recommendations that go beyond the evidence,” she said.

“An additional problem is when we consider the issue of obesity more broadly and consider public health resources and how medicine is being used to deal with problems downstream,” she said. “This model leaves it to individuals to access and take medication as treatment, when we should be thinking about prevention of obesity and food as a population issue.”

In April the think tank the Institute for Government pointed out that every UK government since 1992 had failed to tackle the ever rising prevalence of obesity. Its report said efforts to improve the food environment had been hampered in part by politicians’ fears over “nanny-statism” and that weight loss drugs such as semaglutide were “not a silver bullet,” because of a lack of data on long term safety and efficacy and that they did not tackle root problems in the food industry.

“We need more supply”

Demand for weight loss drugs has soared since the NICE guidelines were published. But in July supply problems prompted the government to ask doctors to stop prescribing them for weight loss because shortages were creating “serious clinical implications” for patients with type 2 diabetes.­­

Naveed Sattar, honorary consultant and professor of metabolic medicine at the University of Glasgow, said, “We’ve already been told that we can’t get semaglutide for another year or so . . . They have vastly underestimated the demand for these drugs in a whole variety of areas, and that’s led to problems of supply for lots of our NHS patients. We need more supply of a range of these drugs going forward.”

In the NHS liraglutide must be provided through tier 3 weight management services, which are available to only around half of the population, researchers said. To be eligible patients must have a BMI of 35 or more or 32.5 for people of south Asian, Chinese, black African, or African-Caribbean origin. Patients must also have pre-diabetes, a high risk of cardiovascular disease, and be unable to undergo weight loss surgery.

In contrast, getting these drugs privately seems to be much less controlled. People can apply through online medical services and must show only that they have a BMI≥30 or a BMI of 27-30 and another weight related comorbidity such as high blood pressure, high cholesterol concentrations, or sleep apnoea. The cost of the treatment through such services is around £240 [$307] a month.

Future role in prevention?

In the absence of effective environmental or societal measures to halt the rise in obesity, Sattar believes that GLP-1 receptor agonists could have a role in preventing overweight and obesity if trials proved them effective.

One such study is the much anticipated Select trial, which is comparing once weekly semaglutide with placebo for preventing cardiovascular events in people with cardiovascular disease who are overweight or obese but do not have diabetes. More than 17,500 people are enrolled in the study, which is expected to report this year.

“If it’s positive and the safety is good, it could have a potentially huge impact,” Sattar said. “You are potentially giving patients living with a cardiovascular disease and excess weight more options in terms of not only lowering the risk of heart attacks and strokes but giving them other benefits in preventing diabetes, preventing other complications, making them feel better, and improving quality of life, which statins and anticlotting agents don’t generally do.”

However, previous trials have indicated that most people experience adverse events while taking these drugs. In the Step 5 trial over eight in 10 (82.2%) patients taking semaglutide but just over half (53.9%) in the placebo group had gastrointestinal disorders such as nausea, diarrhoea, vomiting, and constipation. Most events were “mild-to-moderate and transient,” the study said. Just under 4% of those receiving the drug but less than 1% in the placebo group discontinued because of adverse events.

Source

Mahase, E. BMJ. (2023, Aug 1). 2023; 382;p1772. News Analysis. Obesity: How long should drug treatment last? https://www.bmj.com/content/382/bmj.p1772