The obesity drugs are here: Major shift in treatment, according to experts
After decades of unsuccessful obesity treatment, researchers are now optimistic. New medicines can probably help many who suffer from the chronic disease.
Just a few years ago, pessimism prevailed in obesity research.
The proportion of people who are overweight or obese is increasing in almost every country in the world. Much of the research shows that lifestyle treatment, which is considered the mainstay of obesity treatment, is of limited help. Surgery is much more effective but involves an invasive intervention in otherwise healthy intestines and a significant risk of serious side effects.
In the last couple of years, however, a different form of treatment has appeared as a promising alternative.
From amphetamines to diabetes medication
Anti-obesity drugs have actually been around since the 1950s but have been associated with numerous problems.
The early drugs, such as amphetamines, produced short-term weight loss but had serious side effects. Medications that came onto the market in the late 1990s were not particularly good either. Orlistat provided very modest results, while sibutramine was withdrawn from the market because it was dangerous for the heart.
But then things started to happen.
In the 2000s, new diabetes medicines with the active substance liraglutide came onto the market. It is similar to the natural hormone GLP-1 that is released from the gut when we eat. The hormone causes the body to secrete more insulin. But as time went on, it also became clear that the medicine had another characteristic side effect: patients lost weight.
This outcome made the researchers wonder if the drug could also be used to help people with obesity to more easily implement a lifestyle change.
In 2017, the results of a large study showed that liraglutide, in addition to preventing diabetes, produced an average weight loss of around five per cent of a person’s weight.
This average weight loss is fairly modest, but still large enough to be able to reduce the risk of some of the adverse health effects that come with obesity.
Today, doctors in Norway can prescribe liraglutide medicines to their obese patients, as one of few countries in the world that does so.
But this is just the beginning. Now similar, but much more effective drugs are on the way, such as medications with the substance semaglutide.
Great effect for adults and youth
Semaglutide was also initially developed to treat diabetes. The substance works in a similar way to liraglutide but has a longer-lasting effect in the body.
Startling results emerged in 2021 from a large study of people who had obesity but not type 2 diabetes. All the study participants received lifestyle treatment, but one group also received semaglutide.
More than half of the participants in the semaglutide group lost more than 15 per cent of their weight. A third lost more than 20 per cent, which is almost as much as patients who undergo gastric sleeve surgery.
The reason for the weight loss was that the participants were less hungry and ate less, as suggested by the lifestyle treatment.
A similar study came out in 2022 that showed that the medicine worked just as well on young people.
“Now we're talking!” says Jøran Hjelmesæth, a professor at the University of Oslo and head of the Morbid Obesity Centre in the Health Region South-East, Vestfold Hospital. He has been researching obesity treatment for many years.
“This is an effect that is really felt,” he says.
Real alternative to bariatric surgery
Hjelmesæth is especially pleased with the good results for young people. Many studies have shown that lifestyle treatment has poor average effectiveness for children and adolescents with severe obesity, even when a lot of resources are invested.
“This group has been very difficult to treat effectively. Even the best programmes with the best therapists don’t produce more than a couple per cent BMI improvement,” he says.
The only method that has shown greater effectiveness so far is bariatric surgery. The average reduction has been as high as 30 per cent of patients’ body weight in a year. The emerging medications that now can provide a 12-13 per cent average reduction represent a real alternative to bariatric surgery.
And yet we may only be at the beginning of this development.
Even more effective drugs in sight
Earlier this year saw the results from a trial of yet another new medicine. Researchers tested tirzepatide, which combines GLP-1-like substances with substances that resemble another hormone from the gut. The result was even better than for semaglutide.
Forty per cent of the study participants who received the highest dose achieved at least a 25 per cent weight loss.
“With such good results, a lot of people will think that’s good enough and that they don't need surgery,” says Hjelmesæth.
He also believes that even more medicines may be in store.
“The industry has been creative, and there are lots of new potential medications in the works,” he says, but he warns that it’s by no means certain that all of them will succeed.
It is normal for possible drugs to be less promising than initially thought, for example because they have unexpected side effects.
Medication might be for life
It is also important to be aware that the new obesity drugs do not change the underlying disturbances in regulating appetite. This means that hunger will probably return if people stop taking the drugs.
Many people may have to take such medication permanently to maintain effectiveness.
But in this regard much less is known. We don’t know, for example, whether the effect of the medication will decrease over time. Studies have shown that the substances have an effect for up to a couple of years, but so far no data are available on longer use.
Hjelmesæth believes it will be possible to use the medicines for long periods, even for life if necessary, if future studies show that they maintain their effectiveness.
“These medicines have been tracked over many years in people with type 2 diabetes, and they’ve proven to be very safe,” he says.
Such long-term treatment with medication is used for many other chronic problems, like high blood pressure.
Hjelmesæth nevertheless stresses that the new drugs are not miracle cures for obesity.
“These medicines won’t solve the obesity epidemic, but they’re a new tool for the toolbox. They’ll be good aids for a lot of people with severe obesity,” he says.
Paradigm shift in obesity treatment
Many obesity researchers would no doubt agree.
Hjelmesæth says that results from the youth study on semaglutide were presented and generated great enthusiasm at last year’s Obesity Week, a major conference for obesity researchers.
“The atmosphere has steadily improved as new medicines have emerged,” he says.
The enthusiasm is also evident in several scientific articles from the past year.
“The future of obesity pharmacotherapy is bright,” Timothy Garvey, a professor from the University of Alabama at Birmingham, wrote in the Journal of Clinical Endocrinology and Metabolism in 2022.
Both he and Hjelmesæth describe what is happening in obesity treatment as a clear paradigm shift.
These medications provide many obese people with enough weight loss to significantly reduce the risk of diseases that often accompany obesity, such as type 2 diabetes, cardiovascular disease, sleep apnoea and fatty liver, writes Garvey.
In addition, we now actually have drugs that target one of the basic physiological reasons some of us develop obesity.
Disturbances in the reward system
Obesity is a chronic disease driven by disturbances in regulating hunger and satiety. Dysregulated mechanisms in the hormonal system and central nervous system lead to overeating and fat storage, Garvey writes.
The WHO, the American CDC health agency, the European Commission and a number of medical organizations now all define obesity as a chronic disease.
Hjelmesæth confirms Garvey's statement.
“Of course some people put on weight due to bad habits – like drinking two litres of juice a day. Then they switch to water or soft drinks and rapidly lose weight,” he says.
But many people with severe obesity have a dysregulated reward system.
“They’re hungrier and have to eat more to feel satisfied.”
Genes play a role
These characteristics are partly determined by genetics. Scientists have identified hundreds of genes that each contribute a little piece of the resulting traits.
“A large English study showed that the ten per cent of the population who have the most unfavourable composition of such gene variants weigh on average about 13 kilograms more than the ten per cent with the most favourable composition,” says Hjelmesæth.
In this sense, obesity is not about individuals lacking willpower, but that they will need an unusually great amount of willpower to be able to resist the strong craving for food.
And this is where the new medications come in. They reduce the unrelenting hunger and make it possible for a person to change their lifestyle and eat less.
Translated by: Ingrid P. Nuse
About Jøran Hjelmesæth and Timothy Garvey
- Jøran Hjelmesæth has received speaking fees and participated in advisory forums under the auspices of Novo Nordisk and is an examiner in clinical studies for Novo Nordisk. Novo Nordisk is a manufacturer of medicines with liraglutide and semaglutide.
- Timothy Garvey has participated in advisory forums for several pharmaceutical companies without payment. He has done the same for two non-profit organizations. Through his university, Garvey has also taken part in major clinical studies for several pharmaceutical companies, including Novo Nordisk.
Read the Norwegian version of this article at forskning.no