A new Eli Lilly analysis found that its daily GLP-1 pill, Foundayo (orforglipron), was linked to slightly more weight loss and blood sugar lowering than the higher 25 mg dose of oral semaglutide in adults with type 2 diabetes. At 52 weeks, people on Foundayo 17.2 mg lost 1.5% more body weight and lowered A1C by 0.3 percentage points more, according to Lilly's release on the indirect comparison. The comparison was indirect, meaning the two drugs were never tested against each other in the same study.
The 25 mg semaglutide tablet is the dose sold in the U.S. as the Wegovy pill for weight management. For people deciding between two daily pills, the gap is small enough that dosing routines, stomach side effects, and cost may matter as much as the efficacy numbers.
Lilly framed the result cautiously. "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," said Dr. Rachel Batterham, senior vice president of medical innovation and external engagement at Lilly Cardiometabolic Health.
New Numbers Beyond the Earlier Head-to-Head Trial
MedicalDaily previously reported that orforglipron outperformed lower-dose oral semaglutide in ACHIEVE-3, a head-to-head trial of 1,698 adults with type 2 diabetes. That study compared orforglipron only with the 7 mg and 14 mg semaglutide tablets sold as Rybelsus for diabetes. At the highest doses, Lilly reported that orforglipron lowered A1C by 2.2 percentage points versus 1.4 points for semaglutide, with average weight loss of 19.7 pounds versus 11.0 pounds.
What is new is the comparison with the stronger 25 mg semaglutide dose. Lilly compared ACHIEVE-3 results with data from PIONEER PLUS, a separate trial that tested oral semaglutide doses including 25 mg. The results were adjusted for sex, age, starting A1C, and starting weight, and the analysis was presented at the EASD 2026 Annual Meeting in Milan.
Lilly reported that additional analyses gave consistent results, with Foundayo showing 1.5% to 2.4% greater weight loss and 0.3 to 0.6 points more A1C reduction. ACHIEVE-3 tested orforglipron capsules at 12 mg and 36 mg, which correspond to the 9 mg and 17.2 mg Foundayo tablets now sold in the U.S. That is why earlier reports on the trial list different dose numbers.
Limits of Comparing Two Separate Trials
Indirect comparisons can be useful when head-to-head data do not exist, but they have real weaknesses. The two trials enrolled different people at different times under different conditions, and adjusting for a few characteristics cannot remove every difference. Batterham acknowledged the limitation. "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," she said.
Lilly's figures are also based on what would have happened if participants stayed on treatment without adding other diabetes drugs, not on real-world use with missed doses and dropouts. The analysis was conducted by Lilly and released through a company announcement and a meeting presentation.
Approval status adds another layer. Foundayo was approved by the FDA on April 1, 2026, for weight management in adults with obesity or overweight with weight-related health problems, and is still being studied for type 2 diabetes. Lilly's release notes that the 25 mg semaglutide dose is not approved in the U.S. for type 2 diabetes, though Novo Nordisk has applied for that approval. The Wegovy pill was approved as the first oral GLP-1 for weight management in December 2025, and it is also approved to lower the risk of heart attack, stroke, and cardiovascular death in certain adults with heart disease. For now, both pills are approved in the U.S. for weight, not blood sugar control.
Pill Routines, Stomach Side Effects, and Monthly Costs
The daily routines differ sharply. Lilly says Foundayo can be taken any time of day without food or water restrictions. The Wegovy pill must be taken in the morning on an empty stomach with a sip of water, followed by a 30-minute wait before eating or drinking, NPR reported at approval.
Side effects are a meaningful trade-off. In the ACHIEVE-3 trial published in The Lancet, stomach-related side effects affected 58% to 59% of people on orforglipron versus 37% to 45% on semaglutide. About 9% to 10% stopped orforglipron because of side effects, compared with 4% to 5% on semaglutide. The researchers also reported a larger average rise in pulse with orforglipron (3.7 to 4.7 beats per minute) than with oral semaglutide (1.0 to 1.5 beats per minute), which may be worth raising for people with heart rhythm concerns.
Cost and coverage vary widely by plan, dose, and whether a person pays cash. Novo Nordisk said the starting dose of the Wegovy pill would cost about $149 a month without insurance, ABC News reported. Foundayo's self-pay price also starts at $149 a month for the lowest dose, while the 9 mg to 17.2 mg doses start at $299 a month through Lilly's LillyDirect self-pay pharmacy. Lilly also offers a savings card for people whose commercial insurance covers the drug. Many insurers still exclude weight-loss drugs, so people should check coverage and prior authorization rules before filling either prescription.
Questions for a Doctor Before Choosing Either Pill
This analysis is not a reason to switch medicines on your own. People doing well on a GLP-1 pill already have a treatment that works for them, and any change should be planned with a clinician. Anyone whose A1C or weight goal is not being met has reason to discuss options.
Useful questions include which pill is approved for your condition, whether a morning fasting routine is realistic, and how each drug interacts with other medicines. Lilly's safety information says birth control pills may not work as well while taking Foundayo, and a doctor may recommend another type of birth control for 30 days after starting the drug and for 30 days after each dose increase. People taking insulin or a sulfonylurea should ask about the risk of low blood sugar.
Severe stomach pain that does not go away, persistent vomiting, or signs of dehydration need prompt medical attention. Developments to watch include full publication of the analysis, FDA decisions on diabetes approval for Foundayo and for the 25 mg semaglutide dose, and any direct head-to-head trial of the two pills.
Key Questions Answered
What is new?
A Lilly analysis compared Foundayo 17.2 mg with oral semaglutide 25 mg in adults with type 2 diabetes and found 1.5% more weight loss and 0.3 percentage points more A1C lowering at 52 weeks.
Was it a head-to-head trial?
No. It compared results from two separate trials, which makes the findings less certain than a direct trial.
Is Foundayo approved for diabetes?
Not yet. It is FDA-approved for weight management and is being studied for type 2 diabetes.
Which pill is easier to take?
Foundayo has no food or water rules. The Wegovy pill must be taken on an empty stomach in the morning, followed by a 30-minute wait before eating or drinking.
Which has more side effects?
In the ACHIEVE-3 trial, stomach side effects and stopping treatment because of side effects were more common with orforglipron than with lower-dose oral semaglutide.
Should I switch pills?
Not without talking to your doctor. The differences were modest, and routine side effects and cost may matter as much as the efficacy results.
Published by Medicaldaily.com
