Lilly publishes full ATTAIN-1 results for its oral GLP-1 pill orforglipron

Eli Lilly published complete results from ATTAIN-1, a Phase 3 trial of its investigational oral GLP-1 pill orforglipron, on Sept. 16, 2025, showing that adults with obesity lost more weight on the drug than on placebo over 72 weeks ^[1][2]. The findings appeared in The New England Journal of Medicine and were presented the same day at the European Association for the Study of Diabetes annual meeting ^[1].

Orforglipron is a once-daily pill, not an injection. Lilly describes it as a small-molecule, non-peptide GLP-1 receptor agonist that can be taken at any time of day without restrictions on food or water intake ^[1]. It is not approved for sale. Lilly is studying it for obesity, type 2 diabetes, obstructive sleep apnea and hypertension in adults with obesity ^[1].

ATTAIN-1 randomized 3,127 adults with obesity, or overweight with at least one weight-related condition such as hypertension, high cholesterol, obstructive sleep apnea or cardiovascular disease. None of them had diabetes ^[1][2]. Participants received 6 mg, 12 mg or 36 mg of orforglipron, or a placebo, for 72 weeks alongside a balanced diet and exercise. Lilly says it is the first Phase 3 study in this population to use a healthy diet rather than a reduced-calorie diet as the background ^[1]. Everyone assigned to the drug started at 1 mg and increased the dose in steps every four weeks until reaching their assigned dose ^[1].

The journal reported the treatment-regimen estimand, which estimates the average effect regardless of whether people stayed on the drug or started other weight treatments. Under that analysis, average body weight fell 7.5% at 6 mg, 8.4% at 12 mg and 11.2% at 36 mg, compared with 2.1% on placebo. All three comparisons with placebo were statistically significant ^[2]. Under the efficacy estimand, which estimates what would have happened if every participant had stayed on treatment, the figures were 7.8%, 9.3% and 12.4% (about 27.3 pounds at 36 mg), compared with 0.9% for placebo ^[1][3].

Among people taking 36 mg, 59.6% lost at least 10% of their body weight, 39.6% lost at least 15% and 20.1% lost at least 20%, compared with 8.6%, 3.6% and 1.6% on placebo under the efficacy estimand ^[1]. Under the treatment-regimen estimand, those same thresholds were 54.6%, 36.0% and 18.4%, versus 12.9%, 5.9% and 2.8% on placebo ^[2].

Waist circumference fell 11.1 cm (4.4 inches) at the highest dose versus 2.1 cm (0.8 inches) on placebo, systolic blood pressure fell 6.7 mm Hg versus 0.8 mm Hg, non-HDL cholesterol fell 8.5% versus 1.4%, and triglycerides fell 21.6% versus 4.8%, all under the efficacy estimand ^[1]. In a pre-specified exploratory analysis, the 36 mg dose reduced high-sensitivity C-reactive protein, a marker of inflammation, by 47.7% ^[1]. Among 1,127 participants who had prediabetes when the study began, up to 91% of those taking orforglipron reached near-normal blood sugar by week 72, compared with 42% on placebo. Lilly notes that result was not controlled for statistical error ^[1].

The most commonly reported side effects were gastrointestinal and generally mild to moderate, consistent with the GLP-1 class, according to Lilly and the journal ^[1][2]. Nausea was reported by 28.9%, 35.9% and 33.7% of people on 6 mg, 12 mg and 36 mg, versus 10.4% on placebo; constipation by 21.7%, 29.8% and 25.4% versus 9.3%; diarrhea by 21.0%, 22.8% and 23.1% versus 9.6%; and vomiting by 13.0%, 21.4% and 24.0% versus 3.5% ^[1]. Between 5.3% and 10.3% of people on the drug stopped treatment because of side effects, compared with 2.7% on placebo ^[1][2]. No liver safety signal was observed ^[1].

Why it matters for patients

Orforglipron is being developed as a once-daily oral GLP-1, and these results suggest a pill in this drug class can produce average weight loss and improvements in blood pressure, cholesterol, triglycerides and an inflammation marker ^[1]. That matters to people who prefer a pill to an injection, although the drug is still investigational and no approval or launch date has been announced ^[1].

The results are averages, and individual outcomes varied widely: at the 36 mg dose, 59.6% of participants lost at least 10% of body weight, which means a substantial share did not reach that mark ^[1]. ATTAIN-1 did not compare orforglipron against another GLP-1 medicine, so how it compares with approved products has not been reported. Cost, insurance coverage and how the drug would be positioned in treatment have also not been disclosed.

What happens next

Lilly says it is advancing orforglipron toward global regulatory submissions for obesity, with regulatory action expected as early as next year, which would be 2026. A submission for type 2 diabetes is anticipated in 2026 ^[1]. Additional results from the broader ATTAIN program were expected later in 2025 ^[1]. The company has not disclosed a US filing date or an approval date.