New Oral Drug Orforglipron Demonstrates Superior Weight Loss in Diabetes Patients
A groundbreaking clinical trial has unveiled that the daily pill orforglipron may offer a more effective weight loss solution for individuals with type 2 diabetes compared to existing oral semaglutide. This development could pave the way for a convenient non-injection alternative to popular GLP-1 medications like Wegovy and Mounjaro.
Orforglipron vs. Semaglutide: Key Trial Findings
Manufactured by Eli Lilly, orforglipron targets the same GLP-1 receptors as oral semaglutide, functioning to lower blood sugar levels, slow digestion, and suppress appetite. Unlike semaglutide tablets, it does not require administration on an empty stomach, enhancing its ease of use. The Achieve-3 trial, funded by Eli Lilly, involved over 1,500 adults with type 2 diabetes from 131 medical centers across Argentina, China, Japan, Mexico, and the United States.
Participants received either 12mg or 36mg of orforglipron, or 7mg or 14mg of oral semaglutide, over a one-year period. The results were striking: patients on orforglipron lost an average of 6-8% of their body weight, while those on semaglutide experienced a 4-5% reduction. Additionally, orforglipron users recorded lower average blood sugar levels by the trial's conclusion.
Potential Benefits and Challenges
Experts highlight that tablet versions like orforglipron could be transformative due to their simplicity in administration and storage, potentially leading to lower costs in the long run. Tam Fry, chair of the National Obesity Forum, emphasized, "Orforglipron could prove itself as the treatment of choice for the very obese diabetic. Its real bonus is in its straightforward use."
However, the trial also revealed higher discontinuation rates for orforglipron, with 9-10% of participants stopping treatment due to side-effects, primarily gastrointestinal issues, compared to 4-5% in the semaglutide groups. Dr. Marie Spreckley from the University of Cambridge noted, "Higher discontinuation due to adverse events is a key consideration and may have implications for tolerability and adherence in real-world settings."
Regulatory Status and Future Implications
Orforglipron has not yet received approval from regulators in the UK, US, or Europe, though the US Food and Drug Administration is currently reviewing it. Currently, semaglutide remains the only GLP-1 medication available in pill form in the US, marketed as Rybelsus for diabetes treatment. The weight-loss version of Wegovy has recently been approved, but oral semaglutide has shown less efficacy for weight loss compared to injection-based options like Ozempic, Wegovy, or tirzepatide injections such as Mounjaro.
Professor Naveed Sattar from the University of Glasgow commented, "These are important findings. The more effective oral medicines we have to help people with type 2 diabetes lose weight and keep it off, the better." He added that holistic approaches targeting weight, blood sugar, and cardiovascular risk simultaneously are likely to yield the greatest benefits, with incretin-based therapies potentially becoming first-line treatments for type 2 diabetes within the next decade.
Long-term safety, cardiovascular outcomes, and sustained effectiveness remain critical unanswered questions, as the trial lasted only one year. Nonetheless, orforglipron represents a promising step forward in the fight against obesity and diabetes, offering hope for improved patient outcomes through innovative oral therapies.
