Indianapolis – September 29, 2026 -- Eli Lilly and Company (NYSE: LLY) reported that its oral GLP-1 drug Foundayo (orforglipron) at 17.2 mg produced 1.5% greater weight loss and 0.3% greater A1C reduction than oral semaglutide 25 mg over 52 weeks in adults with type 2 diabetes, based on an indirect treatment comparison presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan.
Indirect analysis draws on ACHIEVE-3 and PIONEER PLUS trial data
The comparison, covariate-adjusted for gender, age, baseline A1C and baseline weight, found weight-loss differences ranging from 1.5% to 2.4% and A1C reductions of 0.3% to 0.6% in favor of Foundayo 17.2 mg across multiple statistical methods. The 95% confidence interval for weight loss was -2.7% to -0.2%, and for A1C reduction was -0.6% to -0.1%.
ACHIEVE-3 head-to-head trial already showed Foundayo's edge over lower-dose semaglutide
In the underlying ACHIEVE-3 trial, which randomized 1,698 participants across the U.S., Argentina, China, Japan, Mexico and Puerto Rico, Foundayo 9 mg and 17.2 mg lowered A1C by 1.9% and 2.2%, respectively, compared with 1.1% and 1.4% for oral semaglutide 7 mg and 14 mg. Weight loss reached 14.6 lbs (6.7%) at the 9 mg Foundayo dose and 19.7 lbs (9.2%) at 17.2 mg, versus 7.9 lbs (3.7%) and 11.0 lbs (5.3%) for the semaglutide arms.
Oral semaglutide 25 mg remains unapproved in the U.S. for diabetes
The 25 mg oral semaglutide dose used in the comparison, from Novo Nordisk's PIONEER PLUS trial, is not currently approved in the United States for type 2 diabetes treatment; Novo Nordisk has submitted an FDA application seeking that approval.
Lilly positions Foundayo as a foundational oral therapy for diabetes markets
Rachel Batterham, senior vice president of medical innovation and external engagement at Lilly Cardiometabolic Health, said the results indicate Foundayo may deliver A1C and weight outcomes similar to the 25 mg oral semaglutide dose, combined with dosing flexibility that removes fasting or water restrictions. Deborah Horn of McGovern Medical School at UTHealth Houston noted that comparative data helps clinicians tailor treatment choices to individual patient needs.
Foundayo currently holds FDA approval for weight management, not diabetes
Foundayo is FDA-approved for adults with obesity or overweight with weight-related conditions, taken once daily as a small-molecule, non-peptide oral GLP-1 receptor agonist without food or water restrictions. Orforglipron, discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018, remains under investigation for type 2 diabetes, obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease and stress urinary incontinence. The ACHIEVE Phase 3 program has enrolled more than 6,000 participants across five global registration trials.