Eli Lilly and Company has reported compelling Phase 3 results for its investigational oral GLP-1 receptor agonist, orforglipron, demonstrating superior blood sugar control and weight loss compared with oral semaglutide in adults with type 2 diabetes.

The findings, presented at the 86th Scientific Sessions of the American Diabetes Association (ADA), come from three Phase 3 studies under Lilly’s ACHIEVE clinical program—ACHIEVE-2, ACHIEVE-3 and ACHIEVE-5. 

The results further strengthen Lilly’s position in the rapidly expanding diabetes and obesity treatment market and pave the way for a regulatory submission to the U.S. Food and Drug Administration (FDA) later this quarter.

The most significant results emerged from ACHIEVE-3, the first-ever head-to-head Phase 3 trial comparing two oral GLP-1 receptor agonists in patients with type 2 diabetes. 

The study showed that orforglipron delivered significantly greater reductions in both HbA1c and body weight than oral semaglutide across all primary and key secondary endpoints.

Patients receiving the highest dose of orforglipron (17.2 mg) achieved an average HbA1c reduction of 2.2% at 52 weeks, compared with 1.4% for oral semaglutide 14 mg. The drug also produced average weight loss of 8.9 kg, substantially higher than the 5.0 kg observed with oral semaglutide.

Notably, 37.1% of patients receiving the highest dose of orforglipron achieved HbA1c levels below 5.7%, a threshold considered indicative of normal blood glucose levels, compared with 12.5% of those receiving oral semaglutide.

“ACHIEVE-3 provides the first head-to-head data on oral GLP-1s in type 2 diabetes, with orforglipron showing greater A1C and weight reductions than oral semaglutide, which was tested at approved diabetes doses,” said Dr. Julio Rosenstock, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center and ACHIEVE-3 lead investigator.

“That level of efficacy is reinforced in ACHIEVE-2 and ACHIEVE-5, demonstrating a consistent and robust treatment effect across a wide spectrum of patient populations. These results support a potential shift toward using oral GLP-1 receptor agonist therapies like orforglipron earlier as a foundation of type 2 diabetes care,” he added.

Based on the cumulative data from ACHIEVE-1 through ACHIEVE-5, Lilly plans to submit orforglipron for FDA approval for the treatment of type 2 diabetes by the end of the second quarter under the agency’s Commissioner’s National Priority Review Voucher program.

If approved, orforglipron could emerge as a significant new oral treatment option in the diabetes market, potentially expanding access to GLP-1 therapies beyond injectable formulations while offering strong efficacy in both blood sugar control and weight reduction.