Eli Lilly appears to have regained the lead over Novo Nordisk in the oral cardiometabolic treatment arena, following results from a head-to-head Phase III trial showing its oral type 2 diabetes and weight-loss candidate, orforglipron, outperformed oral semaglutide.
In the ACHIEVE-3 trial (NCT06045221), which compared the glucagon-like peptide-1 receptor agonists (GLP-1RAs) in 1,698 patients with type 2 diabetes, orforglipron met all the primary and secondary endpoints, delivering greater improvements in A1C and weight loss.
Orforglipron lowered A1C by an average of 1.9% (12mg) and 2.2% (36mg) compared to 1.1% (7mg) and 1.4% (14mg) with oral semaglutide, with 37.1% of patients on high-dose orforglipron achieving A1C <5.7% compared to 12.5% on high-dose oral semaglutide.
Orforglipron was also superior to oral semaglutide for weight loss, with orforglipron patients losing 6.7% in the low dose and 9.2% in the high dose compared with 3.7% and 5.3% in low and high dose oral semaglutide – equating to a 73.6% greater relative weight loss at the highest dose comparison.
Cementing its victory, orforglipron showed clinically meaningful improvements across key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure and triglycerides.
Dr. Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, said: "Head-to-head trials are a gold standard for comparing potential treatments. 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.”
The overall safety and tolerability profile of orforglipron was consistent with previous trials, and the most commonly reported adverse events (AEs) were gastrointestinal-related and generally mild-to-moderate in severity.
Detailed results of the ACHIEVE-3 trial will be presented at a future medical meeting and published in a peer-reviewed journal.
Lilly plans to file for approval to the US Food and Drug Administration (FDA) for orforglipron in obesity by the end of 2026 and in type 2 diabetes in 2026.
Eli Lilly and Novo Nordisk showdown continues
This comes after two separate studies by Eli Lilly and Novo Nordisk seemingly tipped the scales in the latter pharma company’s favour.
In 2024, Novo Nordisk trumped Eli Lilly in the subcutaneous GLP-1RA space, with the company announcing that combined sales of Ozempic and Wegovy (semaglutide) brought a total $25bn, while Lilly’s Mounjaro and Zepbound (tirzepatide) generated a combined $16.47bn. However, Lilly’s drugs are growing at a faster rate compared to Novo’s.
The companies remain the top contenders in the GLP-1RA market, which GlobalData predicts will reach over $125bn in the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan) by 2033.
GlobalData is the parent company of Clinical Trials Arena.
