A new oral medication, orforglipron, may offer a more effective and convenient alternative to existing GLP-1 therapies for weight loss, according to results from a recent phase 3 clinical trial. The findings could signal a breakthrough in non-injection treatments for people with type 2 diabetes.
Manufactured by Eli Lilly, orforglipron works by targeting the same GLP-1 receptors as oral semaglutide, reducing blood sugar, slowing digestion, and suppressing appetite. Unlike semaglutide tablets, orforglipron does not require administration on an empty stomach, potentially making it easier to use.
The drug has not yet received regulatory approval in the US, UK, or Europe, although the US Food and Drug Administration (FDA) is currently reviewing it. At present, semaglutide remains the only GLP-1 pill available for diabetes management in the US, sold under the name Rybelsus, with Wegovy serving as its injectable weight-loss counterpart.
Oral GLP-1 therapies are generally less effective for weight loss compared with injections such as Ozempic, Wegovy, or tirzepatide (Mounjaro). However, experts suggest that pill forms could be transformative due to easier administration, storage, and potentially lower costs.
The Achieve-3 trial, funded by Eli Lilly, involved over 1,500 adults with type 2 diabetes across 131 research centers in Argentina, China, Japan, Mexico, and the US. Participants received either 12mg or 36mg of orforglipron, or 7mg or 14mg of oral semaglutide, over 12 months.
Results showed that patients taking orforglipron lost an average of 6-8% of their body weight, compared with 4-5% in the semaglutide group. Blood sugar levels also improved more significantly among the orforglipron users.
However, side effects were a notable factor. Approximately 9-10% of participants discontinued orforglipron due to gastrointestinal issues, compared with 4-5% in the semaglutide groups.
Experts responded cautiously to the findings. Tam Fry, chair of the National Obesity Forum, said, “Orforglipron could establish itself as the treatment of choice for severely obese diabetics. Its main advantage is its straightforward use. When released, careful control will be necessary to prevent unsafe usage.”
Dr. Marie Spreckley, of the University of Cambridge, highlighted that “higher discontinuation due to adverse events, particularly gastrointestinal symptoms, is a key consideration and may affect tolerability and adherence in real-world settings.” She also noted that the trial’s one-year duration leaves questions about long-term safety, cardiovascular outcomes, and sustained effectiveness unanswered.
Professor Naveed Sattar, a cardiometabolic medicine specialist at the University of Glasgow, emphasized the potential impact of more effective oral therapies, saying, “The better our oral options for helping people with type 2 diabetes lose weight and maintain it, the better.” He added that a holistic approach addressing weight, blood sugar, and cardiovascular risk together is likely to yield the greatest benefits, and incretin-based therapies could become first-line treatments in the coming decade, helping some patients achieve years-long diabetes remission.
