ATTAIN-2 succeeds, completing the obesity filing package

Eli Lilly announced on August 26, 2025 that its experimental oral GLP-1 pill, orforglipron, met the main goal and all key secondary goals of the Phase 3 ATTAIN-2 trial in adults with obesity or overweight who also have type 2 diabetes ^[1]. With that result, Lilly said it now has the full clinical data package needed to start global regulatory submissions for obesity ^[1].

ATTAIN-2 was a 72-week, randomized, double-blind, placebo-controlled trial that enrolled more than 1,600 participants across the U.S., Argentina, Australia, Brazil, China, Czechia, Germany, Greece, India, South Korea and Puerto Rico ^[1]. People were assigned in a 1:1:1:2 ratio to orforglipron 6 mg, 12 mg, 36 mg, or placebo, and all had a BMI of 27 or higher plus type 2 diabetes managed with diet and exercise alone or up to three oral diabetes drugs ^[1]. Everyone started at 1 mg daily and stepped up every four weeks to their assigned maintenance dose ^[1].

What the numbers showed

Starting from an average weight of 223.5 pounds, participants on the 36 mg dose lost an average of 10.5% of body weight (22.9 pounds) compared with 2.2% (5.1 pounds) on placebo, using the efficacy estimand — an analysis that estimates results as if everyone had stayed on treatment ^[1]. The 6 mg and 12 mg doses produced 5.5% and 7.8% average loss ^[1]. Half of those on 36 mg (50.1%) lost at least 10% of body weight, and 28.4% lost at least 15%, versus 7.0% and 1.9% on placebo ^[1].

Blood sugar results were also strong. From an average starting A1C of 8.1%, orforglipron lowered A1C by 1.3 to 1.8 percentage points across doses, compared with 0.1 points for placebo ^[1]. On the 36 mg dose, 85.1% reached an A1C below 7% and 75.0% reached 6.5% or lower — at or below the American Diabetes Association's threshold for diagnosing diabetes ^[1]. Lilly also reported improvements in non-HDL cholesterol, systolic blood pressure and triglycerides, and a 50.6% drop in hsCRP, an inflammation marker, on the top dose in an exploratory analysis ^[1].

A second analysis method, the treatment-regimen estimand, which counts everyone regardless of whether they stayed on the drug, showed smaller but still statistically significant effects: 9.6% weight loss (21.2 pounds) on 36 mg versus 2.5% on placebo, and a 1.7-point A1C reduction versus 0.5 points ^[1].

Side effects

Lilly said the safety profile matched the established GLP-1 class, with mostly mild-to-moderate stomach-related side effects ^[1]. On the 36 mg dose, nausea occurred in 36.4% (versus 8.4% on placebo), vomiting in 23.1% (3.8%), diarrhea in 27.4% (15.0%), constipation in 22.4% (7.8%) and indigestion in 10.9% (3.5%) ^[1]. Discontinuations due to adverse events were 6.1%, 10.6% and 10.6% for the 6, 12 and 36 mg doses versus 4.6% for placebo, while overall dropout rates were similar across groups, ranging from 19.1% to 22.3% versus 20.0% for placebo ^[1]. No liver safety signal was seen ^[1].

Why it matters for patients

Orforglipron is a once-daily pill, not an injection, and it is a small molecule rather than a peptide — meaning it can be taken any time of day without restrictions on food or water ^[1]. That is different from Rybelsus, the oral form of semaglutide, which has taking instructions tied to food and water. If approved, Lilly says it is ready to offer a pill it can scale globally ^[1].

It is worth noting what these results are and are not. People with type 2 diabetes typically lose less weight on GLP-1 drugs than people without diabetes, and Lilly described this group as having "increased difficulties losing weight" ^[1]. ATTAIN-2 compared orforglipron against placebo, not against Wegovy, Zepbound or any other GLP-1 medicine, so no direct head-to-head conclusions can be drawn from this trial ^[1].

The drug remains investigational. Price, insurance coverage and U.S. availability are not addressed in Lilly's announcement and are not yet known.

What happens next

Lilly said it would begin global regulatory submissions for obesity in 2025, calling ATTAIN-2 the trigger ^[1]. Full ATTAIN-2 results will be presented at a future medical meeting and published in a peer-reviewed journal; no date was given ^[1]. Only topline numbers are public so far. Lilly is also studying orforglipron for type 2 diabetes, obstructive sleep apnea and high blood pressure in adults with obesity ^[1].