Weight-loss shots and pills such as Wegovy and Mounjaro have the glamour of association with celebrity users, including Oprah Winfrey.
The public has embraced them too, with millions of people taking the medicines in the US.
But amid the enthusiasm for those medications, known as GLP-1s, an older, cheaper anti-obesity drug that might be a better choice for some patients is being ‘overlooked’, a leading expert says.
Contrave, a pill containing naltrexone and bupropion, is FDA approved in the US as a treatment for people with obesity, or who are overweight with weight-related health problems. Available only via prescription from a healthcare provider, it is cheaper than GLP-1s.
In trials, people using Contrave lost around eight percent of their starting weight. That is lower than the amount lost by people using the latest GLP-1s. In studies of Mounjaro, participants taking the highest doses lost around 22 percent of their body weight.
However, not everyone needs to slim down to that extent, says Alexander Miras, a clinical professor of medicine at the University of Ulster in the UK, who specializes in obesity and type 2 diabetes.
‘If someone’s health can improve with an eight percent weight loss, then those people can use the medication,’ he says.
In trials, people using weight-loss medication Contrave lost around eight percent of their starting weight. That is lower than the amount lost by those using the latest GLP-1s
He suggests Contrave might be best used by people with ‘mild obesity’, such as those whose BMI (body mass index) just tips them into that category, or who have mild weight-related complications such as high blood pressure.
‘The cost is reasonable – and it is one of the cheapest obesity drugs on the market,’ he adds.
The average retail price of a month of Contrave is about $740, but can be as low as $200 with discounts. With some insurances, patients may even pay nothing for a prescription.
Meanwhile, a month of Mounjaro costs anywhere between $1,100 and $1,340. Discount programs can reduce that price down to about $1,000 and people with insurance may pay as little as $25 with certain savings programs.
GLP-1s mimic a natural hormone that is released after eating and tells the brain it is full.
Naltrexone is a drug that treats alcohol and opioid addiction – it blocks the brain’s reward systems. Bupropion is an antidepressant that has also been used as a smoking cessation aid, and stimulates brain chemicals such as dopamine that reduce appetite.
Because they work in different ways, putting the two medications together means they can reduce appetite and cravings more effectively than alone.
Both GLP-1s and Contrave target the hypothalamus, part of the brain which, among its other functions, controls energy intake, hunger and fullness (although they work through different receptors).
‘[Contrave] also works in other parts of the brain involved with the pleasure of food – what we call the reward areas of the brain,’ says Professor Miras.
The parts of the brain involved in the processing of reward from alcohol and drugs also process the reward value of food.
While GLP-1s also appear to have some effects in the brain’s reward networks, the evidence is ‘not as well developed as [for Contrave]’, he says.
It makes Contrave ‘particularly good’ for people who have cravings, binge-eating disorders or who eat in response to emotions such as stress.
‘It is the case that all the noise about the GLP-1 agonists has tended to drown out the availability of other pre-existing weight-loss treatments,’ says Penny Ward, a visiting professor in pharmaceutical medicine at King’s College London in the UK.
She says patients should be alert, however, to ‘fairly significant, albeit uncommon, side effects’ in the older drug, the most serious of which include suicidal thoughts.
GLP-1s mimic a natural hormone that is released after eating and tells the brain it is full
Other potential side effects include headaches, irritability and insomnia.
The fact that GLP-1s are tolerated by more people is part of the explanation for them taking off where Contrave did not, says Professor Miras.
The promise of greater weight loss on GLP-1s will also be a draw for many. But a further factor is likely to be that the companies involved in Contrave are much smaller, with smaller marketing budgets, than the pharma giants Novo Nordisk and Eli Lilly behind the blockbuster GLP-1s, he says.
Contrave could potentially be used alongside GLP-1s, as well as instead of them, says Professor Miras – although the financial burden of paying for two medicines ‘might be too much’ for many patients.
He is worried about tunnel vision in the field that focuses on GLP-1s at the expense of other innovations.
‘There is more to life than GLP-1s,’ he says. ‘Yes, they are a fantastic group of medications. They are going to be with us for decades to come and they are evolving.
‘But we need to be a bit more creative. We need to be looking at other molecules, other targets that can be used in order to develop new medications.’
There are a few in the pipeline, he says – but nothing likely to become available in the next few years.
‘GLP-1 medicines have transformed obesity treatment and the excitement around them is justified: they are highly effective, generally well tolerated, and can bring health benefits beyond weight loss. But they are not the whole story,’ says Dr Bruno Halpern, president of the World Obesity Federation, a global charity which promotes research into and policies to target obesity.
‘Older medicines that work in different ways can still be valuable for people who don’t respond to GLP-1s, cannot tolerate them, cannot access them or simply need a different approach. Expanding access to GLP-1s should remain a priority but we shouldn’t forget that obesity treatment needs more than one tool.’
