A new indirect analysis suggests that Lilly’s oral GLP-1 pill Foundayo could offer marginally better weight loss and blood sugar control than the highest tested dose of oral semaglutide, raising questions about competitive advantages ahead of direct comparison trials.
Eli Lilly has said a new indirect analysis suggests its once-daily GLP-1 pill Foundayo, also known as orforglipron, may deliver slightly stronger weight loss and blood sugar reduction than the highest tested oral semaglutide tablet in adults with type 2 diabetes. Presented at the European Association for the Study of Diabetes meeting in Milan, the comparison linked Foundayo 17.2 mg with 1.5% greater weight loss and a 0.3 percentage-point larger drop in A1C after 52 weeks than oral semaglutide 25 mg, although the two medicines were not tested against each other in the same trial.
The result adds a new layer to a picture that was already beginning to favour Lilly’s pill. In the earlier ACHIEVE-3 study, orforglipron outperformed the lower semaglutide doses used for diabetes treatment, with Lilly reporting a larger reduction in A1C and greater average weight loss. The latest analysis went further by comparing ACHIEVE-3 with PIONEER PLUS, a separate oral semaglutide trial that included the 25 mg dose, allowing Lilly to estimate how the two drugs might stack up at their stronger settings.
Lilly said the findings were adjusted for factors including sex, age, starting A1C and starting weight. The company also reported that additional analyses pointed in the same direction, with Foundayo producing between 1.5% and 2.4% more weight loss and 0.3 to 0.6 percentage points more A1C reduction. Still, the company acknowledged the limitations of comparing two different trials rather than running a direct head-to-head study, and said that such indirect approaches can only go so far in controlling for differences between patient groups and study conditions.
Rachel Batterham, senior vice-president of medical innovation and external engagement at Lilly Cardiometabolic Health, said in a statement that the indirect comparison suggested Foundayo may deliver A1C and weight lowering similar to oral semaglutide 25 mg. She also said direct trials remain the best way to compare medicines, but that indirect data can still provide useful information when those studies do not yet exist.
For patients, the choice is not likely to rest on efficacy alone. Foundayo can be taken at any time of day without food or water restrictions, while oral semaglutide’s 25 mg tablet must be taken in the morning on an empty stomach, followed by a wait before eating or drinking. Side effects also matter: in ACHIEVE-3, stomach-related adverse effects were more common with orforglipron, and more people stopped treatment because of them. Lilly also reported a larger average rise in pulse with orforglipron, which may be relevant for people with heart rhythm concerns.
The commercial picture is equally important. Foundayo was approved by the US Food and Drug Administration on 1 April 2026 for weight management, not diabetes, and it remains under study for type 2 diabetes. Lilly said its lower-dose self-pay option starts at $149 a month, with higher doses costing more, while Novo Nordisk’s oral semaglutide pricing and access rules vary by indication and insurance coverage. For now, the comparison is a useful signal rather than a reason for patients to switch drugs on their own; clinicians will still need to weigh approval status, dosing convenience, side effects, cost and the need for tighter blood sugar control.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
