Participants taking the oral GLP-1 agonist orforglipron maintained more than 70% of their earlier weight loss one year after stopping injectable treatments, according to a study published in the journal Nature Medicine. Those receiving a placebo maintained around 38% to 50% of their weight loss over the same period.

The trial, funded by manufacturer Eli Lilly, included 376 participants in the United States who had been receiving tirzepatide or semaglutide injections for more than a year and had successfully lost weight. Participants stopped the injections and were randomly assigned to receive either orforglipron or a placebo daily for one year without knowing which they were taking.

Among participants who had been using tirzepatide, those taking orforglipron maintained 74.7% of their weight loss after one year, compared with 49.2% of those taking the placebo. Among participants who had been using semaglutide, those on orforglipron maintained 79.3% of their weight loss, compared with 37.6% in the placebo group. Common side effects of orforglipron included nausea, constipation, or diarrhoea, most of which were mild.

Orforglipron, manufactured by Eli Lilly, is a GLP-1 agonist that lowers blood sugar levels, slows digestion, and reduces appetite by mimicking a natural hormone that increases feelings of fullness. The U.S. Food and Drug Administration approved the tablet for weight loss in the United States last month, and it could soon be launched in the United Kingdom. In the U.S., the lowest monthly dose costs around $149, compared with over $1,000 per month for some GLP-1 injections. Novo Nordisk has an oral version of its injectable drug Wegovy that has been approved in the U.S., with a decision pending in the United Kingdom.

"This study reinforces the growing recognition that obesity is a chronic, relapsing disease that often requires ongoing treatment and support," said Dr Marie Spreckley, an expert in weight management research at the University of Cambridge. She said many people do not want to remain on injectable therapy indefinitely due to treatment burden, convenience, travel, storage requirements, cost, or personal preference.

"We still do not know how durable these effects will be over longer periods of time," Spreckley said. She said the possibility of transitioning to an oral therapy while maintaining a substantial proportion of previously achieved weight reduction could represent an important additional option within longer-term obesity care pathways.

Dr Simon Cork, a senior lecturer in physiology at Anglia Ruskin University, said newer oral medications are cheaper to manufacture but do not tend to produce the same level of weight loss seen with injectable medications. He said reductions in blood pressure, lipids, and blood glucose were maintained in patients taking the oral therapy, which could help reduce long-term health risks of obesity such as heart disease.