A once-daily tablet could help people maintain weight loss after stopping popular injectable obesity treatments, according to new clinical research that highlights both the promise and the uncertainties surrounding next-generation weight-loss drugs.
The medicine, orforglipron, is already available in the United States and is being closely watched as a potential future treatment option in the United Kingdom. Early trial results suggest it may reduce a common and frustrating pattern seen with GLP-1 injections, where many patients regain a significant portion of lost weight after stopping therapy.
The findings, published in Nature Medicine and funded by Eli Lilly, suggest that participants who switched to orforglipron after previous treatment with injectable GLP-1 drugs were able to retain most of their weight loss over a 12-month period. Eli Lilly also manufactures Mounjaro, one of the leading injectable obesity treatments currently in use.
Weight regain after discontinuing GLP-1 drugs such as semaglutide or tirzepatide has become a well-recognised issue among clinicians, prompting debate over whether obesity medications should be viewed as short-term aids or long-term treatments that require ongoing use. Some specialists believe sustained therapy may be necessary to maintain benefits.
In the study, 376 adults in the United States who had already achieved significant weight loss using GLP-1 injections were taken off those medicines and randomly assigned to receive either orforglipron or a placebo tablet once daily for a year. Neither the participants nor the researchers knew which treatment was being given.
By the end of the trial period, those taking orforglipron had maintained more than 70% of their earlier weight loss. In contrast, the placebo group kept around 38% to 50%, indicating a much higher degree of weight regain when no active drug was used.
The treatment works by acting on the same hormone pathway targeted by GLP-1 injections. It mimics a naturally occurring hormone that helps regulate appetite, increasing feelings of fullness and reducing hunger, which in turn can lower calorie intake over time.
Side effects were generally reported as mild and consistent with other drugs in the same class, with nausea, constipation, and diarrhoea among the most common complaints.
Experts say the results reinforce the idea that obesity behaves as a chronic and relapsing condition that often requires long-term management. Dr Marie Spreckley of the University of Cambridge, who was not involved in the study, said oral treatments could appeal to patients who prefer pills over injections, although the long-term durability remains unclear. She said, “We still do not know how durable these effects will be over longer periods of time.”
“This study reinforces the growing recognition that obesity is a chronic, relapsing disease that often requires ongoing treatment and support,” she added.
Questions remain over cost and access. While orforglipron is reported to be cheaper than many injectable alternatives in the United States, UK pricing has yet to be determined.
Meanwhile, competition in oral weight-loss treatments is increasing, with other pharmaceutical companies also developing tablet versions of GLP-1 drugs as demand for obesity therapies continues to rise globally.