Complete ATTAIN-1 results published in NEJM and presented at EASD

Eli Lilly released the complete results of its Phase 3 ATTAIN-1 trial of orforglipron, an investigational once-daily oral GLP-1 pill, on September 16, 2025. The data were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting and published the same day in The New England Journal of Medicine ^[1][2].

The trial randomized 3,127 adults with obesity, or overweight plus a weight-related condition such as high blood pressure, abnormal cholesterol, obstructive sleep apnea or cardiovascular disease. None had diabetes. Participants took 6 mg, 12 mg or 36 mg of orforglipron, or placebo, for 72 weeks, alongside exercise and a balanced, healthy diet rather than a reduced-calorie diet ^[1]. Average starting weight was 103.2 kg (227.5 lbs) with an average BMI of 37.0 ^[1].

What the numbers show

Results are reported two ways. The "efficacy estimand" estimates what happens if people stay on the drug; the "treatment-regimen estimand" counts everyone regardless of whether they stopped ^[1]. Under the efficacy estimand, average weight change at 72 weeks was −7.8% on 6 mg, −9.3% on 12 mg and −12.4% (27.3 lbs) on 36 mg, versus −0.9% on placebo ^[1]. Under the treatment-regimen estimand — the primary analysis in the NEJM paper — the figures were −7.5%, −8.4% and −11.2%, versus −2.1% for placebo (P<0.001 for all comparisons) ^[2].

That gap matters when reading the responder rates. Lilly's release highlights that 59.6% of people on 36 mg lost at least 10% of their body weight and 39.6% lost at least 15%, with 20.1% losing at least 20% — those are efficacy-estimand numbers ^[1]. The NEJM abstract reports the same milestones for the 36 mg group as 54.6%, 36.0% and 18.4%, compared with 12.9%, 5.9% and 2.8% on placebo ^[2]. Both sets come from the same trial; they simply answer slightly different questions.

Beyond weight, the 36 mg dose lowered waist circumference by 11.1 cm (4.4 inches) from an average baseline of 112.4 cm (44.25 inches), cut systolic blood pressure by 6.7 mm Hg from a baseline of 125.5 mm Hg, reduced triglycerides by 21.6% and non-HDL cholesterol by 8.5% ^[1]. In a pre-specified exploratory analysis, high-sensitivity C-reactive protein, an inflammation marker, fell 47.7% on the top dose ^[1]. Among the 1,127 participants who had prediabetes at baseline, up to 91% of those on orforglipron reached near-normal blood sugar by week 72, compared with 42% on placebo — though Lilly notes this analysis was not controlled for statistical error across multiple comparisons ^[1].

Side effects were mostly digestive and mostly mild to moderate. Nausea occurred in 28.9%, 35.9% and 33.7% of the 6 mg, 12 mg and 36 mg groups versus 10.4% on placebo; vomiting in 13.0%, 21.4% and 24.0% versus 3.5%; constipation in 21.7%, 29.8% and 25.4% versus 9.3%; and diarrhea in about 21% to 23% versus 9.6% ^[1]. Stopping treatment because of side effects rose with dose: 5.3%, 7.9% and 10.3%, versus 2.7% on placebo ^[1][2]. Lilly said no liver safety signal was seen ^[1].

Why it matters for patients

Orforglipron is a small-molecule pill, not an injection, and can be taken any time of day without food or water restrictions ^[1]. That differs from oral semaglutide (Rybelsus), and Lilly has framed the drug as something primary care doctors could prescribe broadly and manufacture at scale ^[1]. The sources do not compare orforglipron head-to-head with semaglutide or tirzepatide, so any cross-trial comparison of weight loss is not established here.

The average weight loss at the top dose — roughly 11% to 12% over 72 weeks — sits below what injectable tirzepatide has shown in its own trials, but the sources provided do not include those numbers. Price, insurance coverage and US availability are not addressed in these sources and are not yet known.

What happens next

Lilly said it is moving toward global regulatory submissions for obesity, with regulatory action expected "as early as next year," meaning 2026 ^[1]. A submission for type 2 diabetes is anticipated in 2026 ^[1]. The broader ATTAIN program has enrolled more than 4,500 people across two registration trials, with additional results expected in 2025 ^[1]. Orforglipron is also being studied for obstructive sleep apnea and hypertension in adults with obesity ^[1]. It remains investigational and is not approved in the US.