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Eli Lilly's Orforglipron shows superior results in glycemic control and weight loss compared to oral semaglutide in recent clinical trials.
Lilly’ oral GLP-1 delivered topline results in the phase III clinical trial.
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Eli Lilly and Company announced positive results from its Phase III Achieve-3 clinical trial evaluating Orforglipron’s safety and efficiency compared to oral semaglutide. The trial was conducted over a 52-week span, measuring Orforglipron and oral semaglutide across four active treatment arms assessing glycemic control and weight loss.
"Head-to-head trials are a gold standard for comparing potential treatments," said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. "In this type 2 diabetes trial, Orforglipron, even at the lower dose, outperformed both doses of oral semaglutide in reducing A1C. At the highest dose, Orforglipron helped nearly three times as many participants reach near-normal blood sugar versus the highest dose of oral semaglutide. These results, combined with Orforglipron's once-daily oral dosing and broad scalability, reinforce its potential as a foundational treatment for type 2 diabetes."
Orforglipron achieved its primary endpoint in the trials, lowering A1C by an average of 1.9% for 12mg doses and 2.2% for 36mg doses, compared to the oral semaglutide which lowered A1C by 1.1% for 7mg doses and 1.4% for 14mg. In Orforglipron’s secondary endpoint, approximately 37% of participants administered with Orforglipron’s highest dosage achieved a 5.7% decrease in A1C compared to 12.5% for oral semaglutide. In its secondary endpoints, Orforglipron outperformed oral semaglutide in weight reduction, with participants administered with Orforglipron losing an average of 14.6 lbs with 12mg doses and 19.7 lbs for 36mg doses, compared to 7.9 lbs for 7mg and 11 lbs for 14mg doses of oral semaglutide. Aside from displaying its ability in weight reduction and A1C benefits, Orforglipron also showed its ability to improve cardiovascular risk factors such as non-HDL cholesterol, systolic blood pressure, and triglycerides.
Orforglipron’s safety and tolerability profile in Acheive-3 remained consistent with its previous trial results, with the most common reports of adverse events being gastrointestinal-related, with generally mild-to-moderate in severity. Treatment discontinuation rates caused by adverse events totaled 8.7% for 12 mg doses and 9.7% for 36mg doses of Orforglipron, compared to 4.5% for 7 mg doses and 4.9% for 14 mg doses of oral semaglutide, with no hepatic safety signal being observed for Orforglipron.
Orforglipron is an investigational, once-daily small molecule (non-peptide) oral glucagon-like peptide-1 receptor agonist, with the ability to be taken any time of day, without causing any rescritctions on food or water intake for patients. Orforglipron was originally discovered by Chugai Pharmaceutical Co.,and was later licensed by Lilly in 2018.1 Chugai and Lilly published the preclinical pharmacology data of this molecule together, with Lilly running Phase 3 studies on Orforglipron for the treatment of type 2 diabetes along with weight management in adults with obesity or those overweight with at least one weight-related medical problem.1 Orforglipron is also being studied as a potential treatment for obstructive sleep apnea (OSA) and hypertension in adults with obesity.
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