Lilly Posts Full Phase 3 Results for Oral Orforglipron in ATTAIN-2 Obesity and Type 2 Diabetes Trial

Eli Lilly and Company posted detailed results on ClinicalTrials.gov on September 4, 2026 for ATTAIN-2, a Phase 3 trial of its oral GLP-1 receptor agonist orforglipron in adults with obesity or overweight who also have type 2 diabetes. The trial, registered as NCT05872620 and titled "A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral LY3502970 Compared With Placebo in Adult Participants With Obesity or Overweight and Type 2 Diabetes," was one of two core registration trials, alongside ATTAIN-1, that Lilly has said supported its regulatory filings for orforglipron. Lilly first disclosed ATTAIN-2's topline findings in an August 26, 2025 press release; the ClinicalTrials.gov filing is the first public disclosure of the trial's full participant-flow, secondary-endpoint and adverse-event data.

The trial enrolled 1,613 adults at sites in multiple countries between June 5, 2023 and its primary completion on August 8, 2025. Eligible participants had a body mass index of at least 27 kg/m2 and a diagnosis of type 2 diabetes with HbA1c between 7 percent and 10 percent, on stable background treatment for at least 90 days consisting of either diet and exercise alone or up to three oral antihyperglycemic medications, excluding DPP-4 inhibitors or other GLP-1 receptor agonists. Participants were randomized in a roughly 1:1:1:2 ratio to once-daily oral placebo (630 participants) or orforglipron at a target dose of 6 mg (329 participants), 12 mg (332 participants) or 36 mg (322 participants), with dose escalation from 1 mg over the initial weeks. At baseline, participants averaged 56.8 years of age, 101.45 kg in body weight, and were 53.1 percent male and 46.9 percent female overall.

The trial's co-primary endpoints were percent change in body weight and change in A1C from baseline to week 72. Least-squares mean body weight change was minus 2.21 percent with placebo, compared with minus 5.50 percent at the 6 mg dose, minus 7.78 percent at 12 mg, and minus 10.54 percent at 36 mg. The proportion of participants losing at least 5 percent of body weight was 24.4 percent with placebo versus 49.8 percent, 60.2 percent and 72.8 percent at ascending doses; at least 10 percent weight loss occurred in 7.0 percent of the placebo group versus 23.9 percent, 35.5 percent and 50.1 percent on orforglipron; and at least 15 percent weight loss occurred in 1.9 percent of the placebo group versus 7.3 percent, 17.7 percent and 28.4 percent at the three doses. Waist circumference fell 2.67 cm with placebo versus 5.64 cm, 7.16 cm and 9.16 cm across the ascending doses.

A1C fell by a least-squares mean of 0.14 percentage points with placebo, compared with 1.29, 1.60 and 1.79 percentage points at the 6 mg, 12 mg and 36 mg doses. Fasting serum glucose rose 1.2 mg/dL with placebo but fell 33.0, 41.1 and 45.8 mg/dL across ascending orforglipron doses. The proportion of participants reaching an A1C below 6.5 percent was 10.6 percent with placebo versus 56.2 percent, 67.5 percent and 75.0 percent on orforglipron, and the proportion reaching an A1C below 7.0 percent was 23.0 percent with placebo versus 70.0 percent, 78.0 percent and 85.1 percent. In a prespecified analysis pooling the three active doses, orforglipron reduced systolic blood pressure by 4.90 mmHg versus 1.48 mmHg with placebo, reduced non-HDL cholesterol by 6.41 percent versus 2.95 percent, and reduced triglycerides by 17.59 percent versus 4.70 percent; diastolic blood pressure changes were similar between pooled orforglipron and placebo.

Of the 1,608 participants who received at least one dose, 1,444 completed the study: 552 of 628 on placebo, 287 of 328 on 6 mg, 303 of 331 on 12 mg, and 302 of 321 on 36 mg. Serious adverse events occurred in 55 of 628 participants on placebo (8.8 percent), 24 of 328 on 6 mg (7.3 percent), 34 of 331 on 12 mg (10.3 percent) and 35 of 321 on 36 mg (10.9 percent). Ten deaths were recorded overall: 4 on placebo, 0 on 6 mg, 4 on 12 mg and 2 on 36 mg. The ClinicalTrials.gov posting reports these death counts within its adverse-event tables but does not specify causes of death or an investigator assessment of relatedness to study drug. Non-serious gastrointestinal adverse events rose with dose: nausea was reported in 53 of 628 placebo participants (8.4 percent) versus 117 of 321 on the 36 mg dose (36.4 percent); vomiting in 24 of 628 (3.8 percent) versus 74 of 321 (23.1 percent); constipation in 49 of 628 (7.8 percent) versus 72 of 321 (22.4 percent); and decreased appetite in 18 of 628 (2.9 percent) versus 49 of 321 (15.3 percent), with diarrhea and dyspepsia following similar dose-related patterns.

Orforglipron is a non-peptide, small-molecule GLP-1 receptor agonist taken as a once-daily tablet, distinguishing it from injectable or peptide-based GLP-1 drugs. The FDA approved it under the brand name Foundayo on April 1, 2026 for chronic weight management in adults with obesity, or overweight with weight-related conditions, a decision Lilly has said drew on the ATTAIN Phase 3 program including both ATTAIN-1 and ATTAIN-2. Orforglipron is not yet FDA-approved for type 2 diabetes, the population ATTAIN-2 enrolled; Lilly has said diabetes-specific regulatory submissions, based on its separate ACHIEVE trial program, were planned to follow. This report describes trial-level data from a ClinicalTrials.gov results posting and does not constitute treatment or dosing guidance.