A new oral medication for type 2 diabetes, called orforglipron, has shown promising results in a recent late-stage clinical trial. The study, published on February 26, 2026, in The Lancet, suggests the pill may lead to greater reductions in blood sugar levels and more significant weight loss compared to the currently available oral GLP-1 medication.
The trial, known as Achieve-3, is the first of its kind to directly compare orforglipron (at 12 or 36 mg doses) with semaglutide oral (at 7 or 14 mg doses). Semaglutide is currently the only oral GLP-1 available, and must be taken on an empty stomach. Orforglipron, however, can be taken with or without food, offering a potential convenience for patients. The medication is currently under review by the Food and Drug Administration (FDA) in the United States.
The research, based on data from over 1,500 individuals with type 2 diabetes from research centers and hospitals in Argentina, China, Japan, Mexico, and the United States, followed participants for one year. Those taking orforglipron experienced a greater average reduction in blood sugar levels across both dosages when compared to both dosages of semaglutide.
Participants, who had an average starting weight of 97 kg (approximately 214 lbs), lost an average of 6-8% of their body weight with orforglipron, while those on semaglutide lost 4-5%. These findings are significant as managing weight is a crucial component of diabetes care.
However, the study also noted a higher rate of discontinuation among those taking orforglipron. Between 9-10% of participants in the orforglipron groups stopped taking the medication due to adverse events, primarily gastrointestinal issues, compared to 4-5% in the semaglutide groups.
The 52-week head-to-head study assessed the safety and effectiveness of orforglipron versus oral semaglutide in adults with type 2 diabetes whose condition wasn’t adequately controlled with metformin. According to Eli Lilly and Company, orforglipron demonstrated superiority over oral semaglutide on both the primary and key secondary endpoints, showing “significantly greater improvements in HbA1c” and weight loss.
Researchers suggest orforglipron could be a new therapeutic option for people with type 2 diabetes who prefer a pill over an injection and want to avoid restrictions on food and liquid intake. The study also indicated improvements in key cardiovascular risk factors, including non-HDL cholesterol, HDL cholesterol, VLDL cholesterol, total cholesterol, systolic blood pressure, and triglycerides.
“These data highlight the potential benefits of orforglipron compared to oral semaglutide in type 2 diabetes: greater reduction in HbA1c, greater weight loss, and the ability to take it without timing constraints relative to meals or water,” said Kenneth Custer, Executive Vice President and President of Lilly Cardiometabolic Health. “This combination can make a significant difference for people managing their condition day to day.”
With regulatory submissions already underway internationally and FDA action on obesity expected in the next quarter, the company is focused on making this option available to patients as soon as possible. Orforglipron is an investigational, once-daily small molecule oral glucagon-like peptide-1 receptor agonist.
