Eli Lilly and Company recently announced detailed results from 3 phase 3 trials in the ACHIEVE program evaluating Foundayo (orforglipron), a small molecule oral GLP-1 taken without food or water restrictions, in adults with Type 2 Diabetes (T2D).

In the landmark head-to-head ACHIEVE-3 trial, Foundayo outperformed oral semaglutide across the primary and all key secondary endpoints. In ACHIEVE-2 and ACHIEVE-5, Foundayo met the primary endpoint and key secondary endpoints, delivering superior A1C reduction and weight loss versus dapagliflozin and placebo added to insulin glargine respectively.

Results from ACHIEVE-3, ACHIEVE-2 and ACHIEVE-5 were presented at the American Diabetes Association (ADA) 86th Scientific Sessions. ACHIEVE-3 was previously published in The Lancet, while ACHIEVE-2 and ACHIEVE-5 were published in The Lancet and JAMA, respectively.

Dr. Julio Rosenstock, Clinical Professor of Medicine, University of Texas Southwestern Medical Center and ACHIEVE-3 lead investigator, said, "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. 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."

In ACHIEVE-3, Foundayo 9 mg and 17.2 mg outperformed oral semaglutide 7 mg and 14 mg in the first and only head-to-head phase 3 trial of two oral GLP-1 receptor agonists for Type 2 Diabetes.

Foundayo lowered A1C by an average of 1.9 percent (9 mg) and 2.2 percent (17.2 mg) compared to 1.1 percent (7 mg) and 1.4 percent (14 mg) with oral semaglutide at 52 weeks, a 57.1 percent greater relative reduction at the highest dose comparison.

More patients taking the highest dose of Foundayo achieved an A1C <5.7 percent (37.1 percent vs 12.5 percent), the threshold for normal blood sugar levels. Foundayo also delivered greater weight loss, with patients losing an average of 14.6 lbs (6.7 percent; 9 mg) and 19.7 lbs (9.2 percent; 17.2 mg) compared to 7.9 lbs (3.7 percent; 7 mg) and 11.0 lbs (5.3 percent; 14 mg) with oral semaglutide, a 73.6 percent greater relative weight loss at the highest dose comparison.