An oral obesity treatment developed by U.S. drugmaker Eli Lilly was found to reduce body weight by up to 10% over 72 weeks. Although its weight-loss effect is weaker than injectables, it is expected to draw strong interest in the market because it is easy to take.
A research team led by Professor Deborah Horn of the University of Texas Medical School said in The Lancet on the 20th (local time) that "in adults with both obesity and type 2 diabetes, we administered the oral obesity drug Orforglipron daily for 72 weeks and confirmed weight-loss effects of 5.1% to 9.6% depending on the dose."
Orforglipron is a drug with the semaglutide component that mimics the glucagon-like peptide (GLP)-1 hormone, like Lilly's obesity injection Wegovy. GLP-1 is a hormone secreted by the small intestine after meals that promotes insulin secretion from the pancreas to lower blood sugar and suppresses glucagon, which raises blood sugar. It was originally developed as a diabetes treatment to lower blood sugar, and after its weight-loss effect was confirmed, it was advanced as an obesity treatment.
Eli Lilly said in September that in a clinical trial of adults with obesity but without type 2 diabetes, the group taking a high 36 mg dose of Orforglipron for 72 weeks saw an average 11.2% weight reduction. Although that is lower than the 15% reduction effect of the injectable Wegovy, it drew major attention because it is an oral medication that is convenient for patients to take.
To determine whether patients with both obesity and type 2 diabetes could see the same effect, the researchers recruited 1,613 people with both conditions in 10 countries, including the United States, Australia, China, Germany and Brazil. From June 2023 to February 2024, over 72 weeks, participants were randomly assigned to take Orforglipron 6 mg, 12 mg, 36 mg, or a sham drug (placebo) daily.
Participants' baseline weight was 101.4 kg, and their body mass index (BMI, weight divided by height squared) was 35.6. The World Health Organization (WHO) and the United States consider a BMI of 30 or higher to be obesity. The average hemoglobin A1c was 8.05%. A level of 6.5% or higher is diagnosed as diabetes. A total of 1,414 people completed the trial.
In the trial results, after 72 weeks, the high-dose group lost an average of 9.6%, while the medium- and low-dose groups reduced an average of 7.0% and 5.1%, respectively. In contrast, the placebo group lost only 2.5%.
Professor Stefan Trapp of University College London (UCL) said, "Although Orforglipron is less effective for weight loss than GLP-1 injectables, it still shows it can provide benefits for health and quality of life," adding, "With just a 5% reduction in weight, people can increase activity a little or change lifestyle and reduce risks for other conditions."
According to Horn, those on the high dose also saw hemoglobin A1c decrease by about 2% on average. That means most moved out of the diabetic range. In the placebo group, blood sugar decreased by only 0.1%. About 10% of participants on the medium and high doses stopped the drug due to side effects such as nausea, vomiting or diarrhea, but most side effects were manageable, the researchers said.
Eli Lilly acquired technology from Japan's Chugai Pharmaceutical in 2018 and developed Orforglipron. The company expects to receive approval from the U.S. Food and Drug Administration (FDA) early next year as a treatment for obesity and type 2 diabetes, Horn said.
UCL's Trapp said, "Orforglipron does not require refrigeration and does not require syringes, so it will be cheaper to manufacture, store and deliver to patients than injectable GLP-1 drugs," and added, "Combined with the ability to avoid the inconvenience of injections, it could expand access to GLP-1 class obesity drugs in low- and middle-income countries."
References
Lancet (2025), DOI: https://doi.org/10.1016/S0140-6736(25)02165-8
NEJM (2025), DOI: https://doi.org/10.1056/NEJMoa2511774