Eli Lilly’s oral GLP-1 Foundayo (orforglipron) outperformed oral semaglutide, dapagliflozin, and placebo across Phase 3 ACHIEVE trials, delivering superior HbA1c reductions and weight loss in adults with type 2 diabetes.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Eli Lilly reported detailed results from three Phase 3 ACHIEVE studies evaluating Foundayo (orforglipron), a once-daily oral GLP-1 receptor agonist for adults with type 2 diabetes. The data, presented at the American Diabetes Association (ADA) 2026 Scientific Sessions, included the first head-to-head Phase 3 comparison of two oral GLP-1 therapies and support Lilly’s planned FDA submission for the indication later this month.
Foundayo is a small-molecule, non-peptide GLP-1 receptor agonist that can be taken without food or water restrictions. By activating the GLP-1 pathway, the therapy improves insulin secretion, lowers blood glucose levels, and promotes weight loss. Lilly is positioning the drug as a convenient oral alternative to injectable GLP-1 medicines.
ACHIEVE-3 Establishes Advantage Over Oral Semaglutide
The centerpiece of the ADA presentation was ACHIEVE-3 (NCT06045221), a 52-week study involving 1,698 adults whose diabetes remained inadequately controlled on metformin. The trial marked the first Phase 3 head-to-head evaluation of two oral GLP-1 receptor agonists.
Foundayo met its primary endpoint and outperformed oral semaglutide across all key efficacy measures. At the highest-dose comparison, Foundayo delivered a 57.1% greater relative reduction in HbA1c and a 73.6% greater relative reduction in body weight than oral semaglutide.
The therapy reduced HbA1c by up to 2.2% and body weight by up to 9.2% over 52 weeks. More than three-quarters of patients receiving the highest dose achieved an HbA1c of 6.5% or lower, while over one-third reached HbA1c levels below 5.7%, a range considered consistent with normal glycemic control.
Additional Studies Reinforce Efficacy
Results from ACHIEVE-2 (NCT06192108) and ACHIEVE-5 (NCT06109311) showed similar benefits across different treatment settings.
In ACHIEVE-2, Foundayo outperformed dapagliflozin in adults receiving metformin, producing greater reductions in both HbA1c and body weight. Nearly 70% of patients receiving the highest Foundayo dose achieved an HbA1c of 6.5% or lower.
ACHIEVE-5 evaluated patients whose diabetes remained inadequately controlled despite treatment with insulin glargine. Foundayo significantly improved glycemic control compared with placebo and produced meaningful weight loss despite background insulin therapy, a setting where weight gain is often a clinical concern.
Together, the studies demonstrated consistent efficacy across monotherapy, combination therapy, and insulin-background treatment settings.
Cardiometabolic Benefits and Safety
Beyond glycemic control and weight loss, Foundayo improved several cardiometabolic risk markers, including cholesterol measures, triglycerides, and systolic blood pressure.
The safety profile remained consistent with previous studies and with the established GLP-1 drug class. Gastrointestinal events, including nausea, diarrhea, vomiting, dyspepsia, and decreased appetite, were the most frequently reported adverse events. Treatment discontinuations due to adverse events increased with dose and were primarily driven by gastrointestinal side effects.
Regulatory Pathway and Future Development
The ACHIEVE program comprises five pivotal Phase 3 studies evaluating Foundayo across a broad range of treatment settings in type 2 diabetes. Collectively, the program has demonstrated consistent improvements in glycemic control, weight reduction, and cardiometabolic risk factors.
Supported by results from ACHIEVE-1 through ACHIEVE-5, Lilly plans to submit Foundayo for type 2 diabetes to the U.S. Food and Drug Administration by the end of the second quarter of 2026 using a National Priority Review Voucher.
Beyond diabetes, the company is evaluating Foundayo in several cardiometabolic and obesity-related conditions, including obstructive sleep apnea, hypertension, osteoarthritis knee pain, peripheral artery disease, and stress urinary incontinence. If approved, Foundayo could expand the role of oral GLP-1 therapies across multiple chronic metabolic diseases.
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About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.