Lilly reports Foundayo 17.2 mg outperformed oral semaglutide 25 mg in diabetes indirect comparison

Eli Lilly announced on September 29, 2026 that an indirect treatment comparison found its once-daily pill Foundayo (orforglipron) 17.2 mg was associated with greater weight loss and a larger A1C reduction than oral semaglutide 25 mg in adults with type 2 diabetes ^[1]. The analysis was presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan, Italy ^[1].

An indirect comparison is not a head-to-head trial. Instead, researchers statistically compare results from two separate studies — in this case Lilly's ACHIEVE-3 trial of orforglipron and Novo Nordisk's PIONEER PLUS trial of higher-dose oral semaglutide ^[1].

What the numbers showed

At 52 weeks, people taking Foundayo 17.2 mg lost on average 1.5% more of their body weight than those on oral semaglutide 25 mg (95% confidence interval -2.7% to -0.2%), and their A1C fell 0.3% more (95% CI -0.6% to -0.1%) ^[1]. The main analysis adjusted for gender, age, baseline A1C and baseline weight ^[1]. Using other statistical methods, the gaps ranged from 1.5% to 2.4% for weight loss and 0.3% to 0.6% for A1C ^[1].

Those margins are small, and Lilly's own framing was measured. "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, senior vice president of medical innovation and external engagement at Lilly Cardiometabolic Health, who added that the results "suggest that Foundayo may deliver A1C and weight lowering that is similar to the 25 mg dose of oral semaglutide" ^[1].

The underlying head-to-head study, ACHIEVE-3, randomized 1,698 adults with type 2 diabetes not adequately controlled on metformin to orforglipron 9 mg or 17.2 mg, or oral semaglutide 7 mg or 14 mg, across the US, Argentina, China, Japan, Mexico and Puerto Rico ^[1]. At 52 weeks, orforglipron lowered A1C by an average of 1.9% (9 mg) and 2.2% (17.2 mg), versus 1.1% and 1.4% for oral semaglutide 7 mg and 14 mg ^[1]. Average weight loss was 14.6 lbs (6.7%) and 19.7 lbs (9.2%) with orforglipron, compared with 7.9 lbs (3.7%) and 11.0 lbs (5.3%) with oral semaglutide ^[1].

Two important caveats sit in the fine print. A 25 mg once-daily dose of oral semaglutide is not approved in the United States for type 2 diabetes; Novo Nordisk has submitted an application to the FDA seeking approval of that dose ^[1]. And Foundayo itself is currently FDA-approved for adults with obesity, or some adults with overweight plus weight-related medical problems, alongside a reduced-calorie diet and increased physical activity — not for type 2 diabetes ^[1]. Orforglipron is still being studied in type 2 diabetes and other conditions ^[1].

A separate analysis funded by Novo Nordisk, comparing the two drugs in people with obesity, reached the opposite conclusion, favoring oral semaglutide 25 mg over orforglipron 36 mg on weight loss and treatment discontinuations. Full details of that analysis were not released alongside Lilly's announcement.

Why it matters for patients

Most of the GLP-1 conversation in the US still revolves around injections. Both of these products are pills, and Lilly emphasizes that Foundayo is a small-molecule tablet that can be taken any time of day without restrictions on food and water intake ^[1] — a practical difference from Rybelsus-style oral semaglutide, which has dosing conditions.

But competing manufacturer-sponsored indirect comparisons landing on opposite conclusions is a signal to read these results cautiously. Differences of 0.3% in A1C and 1.5% in body weight are modest, the confidence intervals reach close to zero, and the compared populations and trial designs differ. Until a direct trial pits Foundayo against oral semaglutide 25 mg, the ranking is an estimate, not a settled finding.

Foundayo carries a warning that it may cause thyroid tumors, including thyroid cancer, and it should not be used by people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2 ^[1]. Reported serious risks include pancreatitis, severe stomach problems, dehydration leading to kidney problems, low blood sugar when combined with insulin or a sulfonylurea, allergic reactions, vision changes in people with type 2 diabetes, and gallbladder problems ^[1]. Common side effects include nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache and hair loss ^[1].

What happens next

The FDA decision timeline for oral semaglutide 25 mg has not been disclosed ^[1]. Whether Lilly will seek US approval of orforglipron for type 2 diabetes, and when, has not been reported here; the ACHIEVE program enrolled more than 6,000 people with type 2 diabetes across five global registration trials ^[1].