Eli Lilly's orforglipron pill produced 12.4% weight loss in phase 3 trial

Eli Lilly said on Sept. 16, 2025 that its once-daily pill orforglipron produced an average weight loss of 12.4% at 72 weeks in adults with obesity or overweight, according to full phase 3 ATTAIN-1 results published in the New England Journal of Medicine and presented at the European Association for the Study of Diabetes annual meeting ^[3].

The trial randomized 3,127 adults with obesity, or overweight with at least one weight-related condition such as high blood pressure or sleep apnea, and without diabetes. Average starting weight was 103.2 kg (227.5 lbs) and average BMI was 37.0. Participants in the United States, Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain and Taiwan took one of three orforglipron doses (6 mg, 12 mg or 36 mg) or a placebo for 72 weeks, alongside exercise and a balanced diet rather than a reduced-calorie diet ^[3].

At the 36 mg dose, participants lost an average of 12.4%, or 27.3 lbs, compared with 0.9% for placebo. That figure uses what Lilly calls the efficacy estimand, which estimates results as if everyone stayed on treatment. When everyone is counted regardless of whether they stayed on the drug, the 36 mg result was 11.2% (25.0 lbs) versus 2.1% for placebo ^[3]. That difference in measurement explains why some summaries describe the trial as showing average losses as high as 12.4% ^[1] while others put the range at 7.5% to 11.2% after 72 weeks ^[2].

Other results at the 36 mg dose: 59.6% of participants lost at least 10% of body weight, 39.6% lost at least 15% and 20.1% lost at least 20%, compared with 8.6%, 3.6% and 1.6% for placebo. Waist circumference fell 11.1 cm versus 2.1 cm for placebo. Among 1,127 participants who began the study with prediabetes, up to 91% reached near-normal blood sugar levels, compared with 42% on placebo ^[3].

Gastrointestinal side effects were the most common and were generally mild to moderate. At the 36 mg dose, nausea was reported by 33.7% of participants versus 10.4% on placebo, constipation by 25.4% versus 9.3%, diarrhea by 23.1% versus 9.6% and vomiting by 24.0% versus 3.5%. About 10.3% of people on 36 mg stopped treatment because of side effects, compared with 2.7% on placebo. No liver safety signal was seen ^[3].

The FDA approved orforglipron on April 1, 2026, under the brand name Foundayo, for adults with obesity or adults with overweight plus at least one weight-related condition ^[1][2]. It is a non-peptide small molecule, which is why it absorbs without the food and water rules that apply to oral semaglutide, the Wegovy pill, which must be taken on an empty stomach with a wait of at least 30 minutes before eating, drinking or taking other medicines ^[1][2]. Foundayo comes in six tablet strengths: 0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg and 17.2 mg ^[2]. Self-pay pricing has been reported at $149 to $299 per month depending on dose on one pharmacy platform ^[2], while another guide lists $149 to $349 per month ^[1].

Why it matters for patients

Weight loss with orforglipron appears lower than with injectable options. One guide lists about 14.9% for injectable semaglutide, about 20.9% for tirzepatide and about 15% to 17% for oral Wegovy ^[1]. Ro describes orforglipron as producing up to about 11% average weight loss after 72 weeks ^[2]. The trade-off is convenience and cost: no refrigeration, no fasting window, and a monthly price far below the roughly $1,350 listed for injectable Wegovy ^[1].

A heart benefit has not been tested for orforglipron, while semaglutide has one shown in the SELECT trial ^[1]. Medicare coverage is not yet in place; Foundayo is expected to be available under Medicare Part D from July 2026 at about $50 per month ^[1].

What happens next

Lilly has said it anticipates submitting orforglipron for type 2 diabetes in 2026 ^[3]. The drug is also being studied for obstructive sleep apnea and hypertension in adults with obesity ^[3]. Outside of that, how insurers will cover Foundayo broadly, and whether it will show heart benefits in future trials, has not been reported.