After beating Novo Nordisk’s semaglutide last month, Lilly’s much anticipated oral candidate orforglipron has taken down AstraZeneca’s Farxiga in a head-to-head trial.
Eli Lilly’s oral GLP-1 orforglipron has bested AstraZeneca’s Farxiga in a Phase III diabetes trial, the second head-to-head win for the up-and-coming weight loss drug. The therapy previously beat rival Novo Nordisk’s semaglutide.
The Wednesday readout comes from a pair of late-stage trials called ACHIEVE-2 and ACHIEVE-5. In the former, Lilly compared orforglipron with Farxiga in patients with type 2 diabetes that is inadequately controlled on metformin. ACHIEVE-5 compared the drug with placebo in a similar population.
Orforglipron met the main and secondary goals in both trials, showing significant reduction of A1C, a key diabetes biomarker, and weight loss at 40 weeks. The drug also demonstrated improvements in cardiovascular risk factors. All of this came as no surprise to Lilly, based on results from earlier studies, according to the release.
Lilly did not provide specific weight loss numbers. As for A1C, the highest dose of orforglipron reduced the biomarker by 1.7% in ACHIEVE-2 compared to 0.8% in the Farxiga group. In ACHIEVE-5, the study drug achieved a slightly higher A1C reduction of 1.9%, compared to 0.8% for placebo.
Jeff Emmick, senior vice president of product development at Lilly Cardiometabolic Health, said the results showed that orforglipron was superior to Farxiga, which is commonly used to treat diabetes. “Together, these results reinforce orforglipron’s potential to become a new standard of care for people living with type 2 diabetes,” he said in a statement.
Farxiga, which has several approvals for cardiovascular risk and type 2 diabetes, brought home $7.7 billion for AstraZeneca in 2024.
Lilly likened the tolerability and safety profile to previous studies, noting that the most common adverse events were gastrointestinal and generally mild-to-moderate. There were no liver safety signals observed, a key risk with some oral GLP-1 medicines that has taken down weight loss candidates from Lilly’s peers.
Detailed results will be presented at a future medical meeting, Lilly said.
The ACHIEVE program also included ACHIEVE-3, which compared orforglipron to an oral version of Novo’s weight loss franchise standard bearer semaglutide. The injectable medicine is marketed as Wegovy for weight loss and Ozempic for diabetes. Lilly showed in September a 2.2% reduction in A1C with orforglipron, compared to 1.4% with oral semaglutide. On weight loss, Lilly’s drug achieved 9.2% weight loss at 52 weeks, compared to 5.3% with oral semaglutide.
Lilly has rolled out a major challenge to Novo in the clinic. Besides orforglipron, the company is also running head-to-head trials of its approved weight loss medication, tirzepatide, also known as Zepbound, against semaglutide. In December 2024, Lilly announced that Zepbound elicited greater weight loss than Wegovy, with patients losing 50.3 lbs as compared to 33.1 lbs at 72 weeks.
The final ACHIEVE results will be delivered in the first quarter of 2026; ACHIEVE-4 is comparing orforglipron with standard insulin glargine in patients with type 2 diabetes who are overweight or have obesity, and who have an increased cardiovascular risk.
