Eli Lilly and Co (NYSE:LLY) on Tuesday shared detailed results from the Phase 3 ATTAIN-1 trial, evaluating the safety and efficacy of oral orforglipron in adults with obesity, or overweight with a weight-related medical problem, and without diabetes.
At 72 weeks, all three doses (6 mg, 12 mg, and 36 mg) of orforglipron met the primary endpoint of superior body weight reduction compared to placebo.
In addition, all three doses delivered clinically meaningful results compared to placebo across the key secondary endpoints of body weight reduction (≥10%, ≥15% and ≥20%), and waist circumference reduction.
Results were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine.
In the ATTAIN-1 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo, with participants taking the highest dose losing an average of 27.3 lbs (12.4%) at 72 weeks using the efficacy estimand.
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In key secondary endpoints, 59.6% of participants taking the highest dose of orforglipron lost at least 10% of their body weight, while 39.6% lost at least 15% of their body weight.
Among the 1,127 participants who had prediabetes at the start of the study, up to 91% of those taking orforglipron achieved near-normal blood sugar levels compared to 42% of those taking a placebo at 72 weeks.
Additionally, orforglipron showed clinically meaningful improvements across key cardiovascular risk factors often associated with obesity, including non-HDL cholesterol, systolic blood pressure, and triglycerides. In a pre-specified exploratory analysis, the highest dose of orforglipron reduced high-sensitivity C-reactive protein (hsCRP) levels, a marker of inflammation, by 47.7%.
The most commonly reported adverse events were gastrointestinal-related and generally mild-to-moderate in severity.
Treatment discontinuation rates due to adverse events were 5.3% (6 mg), 7.9% (12 mg), and 10.3% (36 mg) for orforglipron vs. 2.7% with placebo. No hepatic safety signal was observed.
Lilly is advancing orforglipron toward global regulatory submissions for the treatment of obesity, with regulatory action expected to occur as early as next year.
Submission for the treatment of type 2 diabetes is anticipated in 2026.
Price Action: LLY stock is down 1.60% at $752.45 during the premarket session at the last check on Wednesday.
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