Does the obesity drug tirzepatide pull its weight in efforts to improve public health?
▶ Clinical trial offers positive results but experts say lifestyle changes should be the first step in treatment, writes Daniel Bardsley
The global figures for obesity are startling. The World Health Organisation has estimated that there are more than 1.9 billion overweight adults – 39 per cent of the adult population.
Of these, 650 million – or 13 per cent of the adult population – are obese, meaning their body mass index is at least 30.
“When we look at obesity, it’s a growing public health problem,” said Richard Holt, professor in diabetes and endocrinology at the University of Southampton in the UK.
“The number of people now overweight or obese is getting larger. Being overweight is associated with significant medical problems, as well as social problems such as stigma.”
But could the new drug tirzepatide be the answer?
Q
What is tirzepatide and how did it do in clinical trials?
AProduced by the American drug company Eli Lilly, tirzepatide reduces appetite by mimicking the effect of hormones released in the body when a person eats.
Last Thursday, Eli Lilly released the results of clinical trials involving 2,539 patients, some of whom were given five milligram, 10mg or 15mg treatment regimes of the drug.
For the lowest dose, average weight loss was 15 per cent of body weight, while in the 10mg group it was 19.5 per cent. In the 15mg group, the average weight loss was 20.9 per cent. Among patients given a placebo, it was 3.1 per cent.
Dr Jeff Emmick, vice president of product development at Eli Lilly, said the drug was the first to achieve an average weight loss of more than 20 per cent in a late-stage trial.
About two thirds of those on the highest dose lost at least 20 per cent of their body weight.
How does this compare to lifestyle changes?
Mr Holt said diet and lifestyle management – trying to reduce
a person’s calorie intake and increase their energy expenditure – was often the first line of treatment for significantly overweight people.
“There are very, very many diets advertised for the management of obesity. It’s probably fair to say none of them are particularly effective if you look across the whole of the population,” he said.
He would expect people to lose an average of up to 5 per cent with lifestyle management. “It’s not to say lifestyle is not useful – some people respond very well to lifestyle.
“We would expect two out of 10 to lose a significant amount of weight with lifestyle. That leaves eight out of 10 who haven’t lost a significant amount.”
He said that with lifestyle changes, people might find it straightforward to lose weight, but more difficult to maintain weight loss over time.
How does tirzepatide compare to other drugs or surgery?
After lifestyle and dietary changes, the next level of treatment is drug therapy, of which
there are “very few licensed for the management of obesity”, Mr Holt said.
Obesity drugs have often been marketed, only to be withdrawn because of “significant side effects”.
Aside from tirzepatide, another drug is semaglutide, which acts in a similar way. Clinical trial results released a year ago showed it cut body weight by about 15 per cent and produced only modest side effects. About a third of patients lost more than 20 per cent of their body weight.
At the time, it was described as “a game-changer” by a researcher who co-wrote a paper outlining the results. They said it achieved weight loss “no other drug has come close to”.
Semaglutide is used to help people lose weight, but the latest results suggest tirzepatide could be even more effective. With both drugs, side effects appear to be modest.
But Mr Holt said he did not think tirzepatide should be given to everyone.
“Lifestyle interventions are where we should start. With
people with more serious [obesity] or who have tried lifestyle changes and these have been unsuccessful, drug therapies are a successful option,” he said.
“This would be a useful treatment to include in the treatment armamentarium.”
The latest drugs offer a “major, major step forward in the amount of weight loss”, he said.
Beyond administering drugs, the next treatment for obesity is bariatric surgery, a variety of procedures that include having a gastric band placed around the stomach so the patient feels full after eating a smaller amount.
Mr Holt said the results achieved by tirzepatide were “the sort of level you might expect to see with people” who had undergone a type of bariatric surgery.
Prevention is better than cure
While drug treatments are improving, preventing obesity from developing in the first place is often considered to be more effective than trying to
achieve weight loss after a person has become obese.
“Reduction is really difficult because the brain is structured in a way that changing your behaviour takes a long time to settle in your brain,” said Dr Antje Hebestreit, head of the lifestyle-related disorders unit at the Leibniz Institute for Prevention Research and Epidemiology.
“Once you already have these behaviours leading to obesity, to really get rid of them takes a long time … this is why prevention is the favourite approach.”
She said some ways to prevent obesity in adults, such as using phone apps that monitor a person’s diet, physical activity and sleep patterns, may reduce the risk of obesity by 40 to 75 per cent if users adhere to the recommendations.
Interventions are best started early on, especially during childhood, she said.
Parents have a big influence on whether their children become obese, she said, with the mother’s BMI and education level linked to the risk of obesity in her children.