In a significant breakthrough, Eli Lilly’s oral GLP-1 drug orforglipron demonstrated superior blood sugar control and weight loss compared to oral semaglutide in a 52-week phase 3 trial, potentially expanding treatment options for adults with type 2 diabetes.
Eli Lilly’s oral GLP-1 drug orforglipron appears to have delivered stronger blood sugar and weight outcomes than oral semaglutide in a late-stage comparison in adults with type 2 diabetes, according to results discussed in Drug Topics and a related report of the ACHIEVE-3 trial in The Lancet. The finding adds fresh momentum to a programme that could broaden the appeal of GLP-1 medicines if regulators eventually clear the drug for diabetes treatment.
ACHIEVE-3 was a 52-week, randomised, open-label phase 3 study that enrolled 1,698 adults whose type 2 diabetes remained inadequately controlled on metformin. Participants were recruited in the United States, Argentina, China, Japan, Mexico and Puerto Rico and were assigned to one of four oral regimens. Drug Topics reported that orforglipron reduced HbA1c, a measure of long-term blood glucose, by 1.9 percentage points at the lower dose and 2.2 points at the higher dose, compared with 1.1 points and 1.4 points for oral semaglutide.
Weight loss also favoured orforglipron. According to the same report, people taking the Eli Lilly drug lost an average of 14.6lb at the lower dose and 19.7lb at the higher dose, while those on oral semaglutide lost 7.9lb and 11.0lb. A separate summary of the trial in The Lancet likewise said orforglipron was superior to oral semaglutide on both glycaemic control and body weight over 52 weeks, reinforcing the overall direction of the findings.
The comparison drew additional context from earlier work on higher-dose oral semaglutide. Novo Nordisk has previously said a 25mg dose lowered HbA1c by 1.9 percentage points and body weight by 7.0kg in its PIONEER PLUS study, although that dose is not yet approved in the United States for type 2 diabetes. Drug Topics also noted that Eli Lilly has presented orforglipron as a once-daily, non-peptide oral GLP-1 receptor agonist that can be taken without food or water restrictions, a practical advantage that could matter to patients who struggle with the dosing rules attached to some oral diabetes medicines.
Safety remains an important caveat. The update said gastrointestinal side effects were the most common adverse events in ACHIEVE-3, and more people stopped treatment because of side effects on orforglipron than on oral semaglutide. That means the headline efficacy results may need to be weighed against tolerability if the drug advances further in development and regulators eventually review the data.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
