Eli Lilly’s new oral pill, orforglipron, led to up to 8% weight loss in clinical trials, outperforming existing oral semaglutide alternatives.
As demand for weight-loss treatments grows, pharmaceutical companies are racing to develop more efficient and accessible drugs.
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In addition to the well-known injectable GLP-1 drugs such as Ozempic, Wegovy, and Mounjaro, new oral treatments are entering the market.
The new pill, called orforglipron, is more effective than the alternative oral semaglutide in a recent clinical trial.
Participants on the trial lost an average of six to eight percent of their body weight, compared to four to five percent achieved with the current oral semaglutide drugs, according to the results published in The Lancet.
Injectable versions remain the most popular weight-loss treatments. They have been available since 2014 and their popularity has increased in recent years.
Aiming to increase accessibility and convenience, manufacturers are developing oral pill treatments.
Orforglipron, a daily pill that can be taken without food or water restrictions, is Eli Lilly’s bet to compete with Novo Nordisk, which currently holds the authorisation for the only GLP-1 oral pill in the market.
The company has also developed Zepbound and Mounjaro, injectable treatments for chronic weight management and type 2 diabetes, respectively.
Orforglipron has not yet received market authorisation and is under regulatory review by the United States’ Food and Drug Administration (FDA).
Eli Lilly announced that, if approved, US patients with obesity will be able to access orforglipron starting at $149 (€125.92) for the lowest dose, with additional doses up to $399 (€337), if not covered by insurance.
How was the clinical trial done?
The trial included more than 1,600 people from more than 130 investigation centres in five countries.
All participants had type 2 diabetes and were randomly assigned different orforglipron doses, 12mg, 36mg, or equivalent semaglutide doses over one year.
Approximately 60 percent of participants taking orforglipron lost at least 5 percent of their body weight, compared with about 40 percent in those taking semaglutide.
Around 28 to 44 percent of participants on orforglipron lost 10 percent or more of their body weight, compared to 13 to 21 percent on semaglutide.
For patients with type 2 diabetes, a weight loss of 5-10 percent can improve blood sugar metabolism. Bigger reductions can help reduce the risk of diabetes complications, the study noted.
Orforglipron also reduced blood sugar levels more effectively than semaglutide.
“The more effective oral medicines we have to help people with type 2 diabetes lose weight and keep it off, the better,” said Naveed Sattar, professor of cardiometabolic medicine at the University of Glasgow, who was not part of the study.
“Excess weight is the major driver of type 2 diabetes, and it also contributes to higher blood pressure and abnormal lipid levels,” Sattar added.
Higher adverse effects
While orforglipron increased weight loss benefits, participants also reported higher adverse effects.
Around 9-10 percent of the participants had to stop the treatment due to gastrointestinal issues, compared to about five percent of those taking semaglutide.
Marie Spreckley, a weight management researcher and doctor at Cambridge University, who was not part of the study, noted the adverse events could be a barrier to the pill’s tolerance in real-world settings outside the trials.
“The trial duration was one year and focused on glycaemic and weight outcomes, so longer-term safety, cardiovascular outcomes, and sustained effectiveness remain important unanswered questions”, Spreckley added.
