Foundayo 17.2 mg was associated with 1.5% greater weight loss and 0.3% greater A1C reduction than oral semaglutide 25 mg at 52 weeks

These additional analyses build on findings of the ACHIEVE-3 head-to-head study, where Foundayo 9 mg and 17.2 mg delivered greater A1C and weight reductions than oral semaglutide 14 mg

INDIANAPOLIS, Sept. 29, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide), today announced results from a new analysis showing that Foundayo (orforglipron) 17.2 mg was associated with significantly greater weight loss and better blood sugar control than oral semaglutide 25 mg in adults with type 2 diabetes. The findings are based on an indirect treatment comparison of Foundayo 17.2 mg against oral semaglutide 25 mg, drawing on data from ACHIEVE-3 and PIONEER PLUS.1,2,3,4 Presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, these results add to a growing body of evidence supporting Foundayo's efficacy.

"For someone managing type 2 diabetes, the choice between treatments is a decision that impacts their life every day," said Deborah Horn, D.O., director of the Center for Obesity Medicine at McGovern Medical School at UTHealth Houston. "Having data to help us compare available medications provides clinicians the opportunity to make informed treatment choices that fit each patient's needs."

In an indirect treatment comparison using data from ACHIEVE-3 and PIONEER PLUS, Foundayo 17.2 mg showed significantly greater weight loss and A1C reduction compared to oral semaglutide 25 mg at 52 weeks.5 On average, participants taking Foundayo 17.2 mg lost 1.5% more of their body weight compared to oral semaglutide 25 mg (95% CI -2.7%, -0.2%). Additionally, Foundayo lowered A1C by 0.3% more than oral semaglutide 25 mg (95% CI -0.6%, -0.1%). This analysis was covariate-adjusted for gender, age, baseline A1C and baseline weight. Analyses using different statistical methods produced consistent results, with Foundayo 17.2 mg showing 1.5% to 2.4% greater weight loss and 0.3% to 0.6% greater A1C reduction compared to oral semaglutide 25 mg.

"Head-to-head trials ultimately provide the best comparison of two medicines, but when we don't yet have those data, then other approaches can provide informative data points," said Rachel Batterham, OBE, MBBS, Ph.D., FRCP, senior vice president of medical innovation and external engagement, Lilly Cardiometabolic Health. "Results from this indirect treatment comparison suggest that Foundayo may deliver A1C and weight lowering that is similar to the 25 mg dose of oral semaglutide. These results, paired with simple administration free of fasting or water restrictions, are what make Foundayo a potentially foundational therapy for adults managing type 2 diabetes around the world."

About Foundayo (orforglipron)

Foundayo (orforglipron) is FDA-approved for adults with obesity, or some adults with overweight who also have weight-related medical problems, to reduce excess body weight and maintain weight reduction long term, alongside a reduced-calorie diet and increased physical activity. Foundayo is a once-daily small molecule (non-peptide) oral glucagon-like peptide-1 receptor agonist that can be taken any time of the day without restrictions on food and water intake. Orforglipron was discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018. Orforglipron is being studied as a potential treatment for type 2 diabetes, obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease and stress urinary incontinence. 

About ACHIEVE-3 and ACHIEVE clinical trial program

ACHIEVE-3 (NCT06045221) is a Phase 3, 52-week, randomized, open-label trial evaluating the efficacy and safety of orforglipron compared with oral semaglutide (Rybelsus) in adults with type 2 diabetes inadequately controlled with metformin. The trial randomized 1,698 participants across the U.S., Argentina, China, Japan, Mexico and Puerto Rico to receive either 9 mg or 17.2 mg orforglipron or 7 mg or 14 mg oral semaglutide in a 1:1:1:1 ratio. The primary objective of the study was to demonstrate that orforglipron is non-inferior in A1C reduction from baseline after 52 weeks compared with oral semaglutide when comparing the lower and higher doses.

In ACHIEVE-3, Foundayo lowered A1C by an average of 1.9% (9 mg) and 2.2% (17.2 mg) compared to 1.1% (7 mg) and 1.4% (14 mg) with oral semaglutide at 52 weeks. Foundayo also delivered greater weight loss, with participants losing an average of 14.6 lbs (6.7%; 9 mg) and 19.7 lbs (9.2%; 17.2 mg) compared to 7.9 lbs (3.7%; 7 mg) and 11.0 lbs (5.3%; 14 mg) with oral semaglutide.

The ACHIEVE Phase 3 global clinical development program for orforglipron enrolled more than 6,000 people with type 2 diabetes across five global registration trials.

Endnotes and References

- Rosenstock J, Yabe D, Cox D, et al. Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial. Lancet. 2026 Mar 21;407(10534):1147-1160. https://doi.org/10.1016/S0140-6736(26)00202-3. Epub 2026 Feb 26. PMID: 41765029.

- Aroda V, Aberle J, Bardtrum L, et al. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. The Lancet, 2023; 402, 693-704. https://doi.org/10.1016/s0140-6736(23)01127-3

- Cheng A, Jacobi D, Mojdami D, Li J, Li J, Zhao Y, Terrell K, Liu-Seifert H. Oral orforglipron 17.2 mg versus oral semaglutide 25 mg in adults with type 2 diabetes and BMI ≥25kg/m2: an indirect treatment comparison.

- A 25 mg once-daily dose of oral semaglutide is not approved in the United States for the treatment of type 2 diabetes. Novo Nordisk has submitted an application to the FDA seeking approval of that dose.

- All data referenced in this press release are based on the efficacy estimand. In ACHIEVE-3, the efficacy estimand represents treatment efficacy had all randomized participants remained on study intervention (with possible dose interruptions and/or dose modifications) for 52 weeks without initiating additional antihyperglycemic medications (>14 days of use). In PIONEER PLUS, the corresponding estimand is termed as the trial product estimand in the manuscript.

U.S. FOUNDAYO INDICATION AND SAFETY SUMMARY WITH WARNINGS 

Foundayo (fown-DAY-oh) is a prescription medicine used with a reduced-calorie diet and increased physical activity to help adults with obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off. 

- Foundayo should not be used with other GLP-1 receptor agonist medicines.

- It is not known if Foundayo is safe and effective for use in children.

Warnings – Foundayo may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.

- Do not use Foundayo if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).

- Do not use Foundayo if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

- Do not use Foundayo if you have had a serious allergic reaction to orforglipron or any of the ingredients in Foundayo.

Foundayo may cause serious side effects, including:

Inflammation of the pancreas (pancreatitis). Stop taking Foundayo and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without nausea or vomiting. Sometimes you may feel the pain from your abdomen to your back.

Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Foundayo. Tell your healthcare provider if you have stomach problems that are severe or will not go away.

Dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.

Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Foundayo with medicines that can cause low blood sugar, such as an insulin or sulfonylurea. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness, or feeling jittery.

Serious allergic reactions. Stop using Foundayo and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat.

Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Foundayo.

Gallbladder problems. Gallbladder problems have happened in some people who use Foundayo. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools.

Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Foundayo may increase the chance of food getting into your lungs during surgery or other procedures. Tell your healthcare providers that you are taking Foundayo before you are scheduled to have surgery or other procedures.