Efficacy and safety of oral orforglipron in Japanese participants with obesity disease (ATTAIN-J): a double-blind, randomised, placebo-controlled, parallel-group, phase 3 trial
- Design
- Randomized trial · 238 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all 238 participants were Japanese adults with obesity disease, BMI between 27 kg/m2 and less than 35 kg/m2 with two or more obesity-related health disorders or BMI 35 kg/m2 or higher with one or more, with type 2 diabetes targeted at about 25%; mean age was 54·1 years.
- Could weight loss explain it?
- Not applicablenot_applicable: the co-primary endpoints are mean percentage change in bodyweight and the proportion reaching at least 5% bodyweight reduction, so the outcome is weight itself and no mediation question arises (IN-062).
- Study tier
- Study tier 2MODERATE: a double-blind, randomised, placebo-controlled, parallel-group phase 3 trial with computer-generated allocation, 90% completion and confidence intervals on every bodyweight endpoint. It sits at study tier 2 rather than tier 1 because it randomised 238 participants at 16 Japanese centres and its co-primary endpoints are bodyweight, an intermediate outcome, not clinical events.
- Assessment
- Version 3 · Two independent AI reviews agreed · Nov 6, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
ATTAIN-J randomly assigned 238 Japanese adults with obesity disease and obesity-related health disorders to a once-daily tablet of orforglipron at 6 mg, 12 mg or 36 mg, or to placebo, for 72 weeks, with neither participants nor staff knowing the assignment. Mean age was 54·1 years and 144 (61%) were male. At week 72, mean percentage change in bodyweight was -5·9% (95% CI -7·6 to -4·2) with 6 mg, -8·7% (-10·9 to -6·5) with 12 mg and -7·9% (-10·0 to -5·8) with 36 mg, against -0·6% (-2·1 to 0·8) with placebo (all p<0·0001), and at least 5% bodyweight reduction was reached by 45·6%, 60·8% and 58·8% of participants against 15·2% on placebo. Adverse events were mostly mild-to-moderate gastrointestinal symptoms, with nausea leading five [8%] of 60 participants on 36 mg to discontinue against none on placebo. Eli Lilly and Company funded the trial.
01Findings
What the study reported
- Drugs
- Orforglipron
- Dose
- 6 mg, 12 mg, or 36 mg once daily
- Route
- oral
- Comparator
- placebo
- Treatment duration
- to week 72
- Primary outcome
- co-primary: mean percentage change in bodyweight, and percentage of participants with at least 5% bodyweight reduction, from baseline to week 72
- Effect
- Mean percentage change in bodyweight at week 72: -5·9% with orforglipron 6 mg, -8·7% with 12 mg and -7·9% with 36 mg against -0·6% with placebo, all p<0·0001. At least 5% bodyweight reduction in 45·6% (6 mg), 60·8% (12 mg) and 58·8% (36 mg) against 15·2% on placebo.
- 95% confidence interval
- 95% CI -7·6 to -4·2 (6 mg), -10·9 to -6·5 (12 mg), -10·0 to -5·8 (36 mg) and -2·1 to 0·8 (placebo)
- P value
- all p<0·0001 vs placebo for mean percentage bodyweight change; p=0·0001 (6 mg) and p<0·0001 (12 mg and 36 mg) for at least 5% bodyweight reduction
- Follow-up
- to week 72
- Adverse events
- Adverse events were mostly mild-to-moderate gastrointestinal symptoms. Discontinuation from nausea in one [2%] of 61 (6 mg), one [2%] of 57 (12 mg) and five [8%] of 60 (36 mg) versus none with placebo; from vomiting in two [4%] (12 mg) and one [2%] (36 mg) versus none with placebo.
- Limitations
- A single-country trial of 238 participants over 72 weeks whose co-primary endpoints are bodyweight rather than clinical events; the 36 mg dose produced less weight loss than the 12 mg dose and more discontinuations, 214 of 238 completed, and the manufacturer funded the trial and employs four of the authors.
Who was studied
- Mean age
- 54.1
- Age min
- 18
- Sex distribution
- 144 [61%] males and 94 [39%] females
- Bmi min
- 27
- Obesity status
- required: BMI between 27 kg/m2 and less than 35 kg/m2 with two or more obesity-related health disorders, or BMI 35 kg/m2 or higher with one or more
- Diabetes status
- mixed: type 2 diabetes was one of the qualifying obesity-related disorders, targeted at about 25% of participants
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- obesity disease in Japanese adults
- Sample size
- 238
- Inclusion exclusion
- adults 18 or older, BMI 27 to under 35 with two or more obesity-related disorders or BMI 35 or higher with one or more, one being hypertension, dyslipidaemia or type 2 diabetes, and at least one unsuccessful dietary attempt to lose weight
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 238
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- to week 72
- Outcome type
- intermediate
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- 95% CIs reported for every bodyweight endpoint with standard errors for the responder analysis; 238 randomly assigned and 214 (90%) completed
- Risk of bias
- not assessed
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Eli Lilly and Company
- Industry funded
- Yes
- Manufacturer
- Eli Lilly and Company
- Sponsor role
- The study funder paid for medical writing and editorial support; no other sponsor role is stated.
- Author conflicts
- All authors report medical writing and editorial support paid for by the study funder, four academic authors report research grants, consulting fees and lecture honoraria from many pharmaceutical companies including Eli Lilly and Novo Nordisk, and four authors are Eli Lilly Japan employees and Eli Lilly shareholders.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly and Company, named in the abstract as the study funder; four authors are Eli Lilly Japan employees and Eli Lilly shareholders, all authors received medical writing and editorial support paid for by it, and four academic authors report its consulting fees or honoraria.
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Orforglipron, a small-molecule, non-peptide, oral GLP-1 receptor agonist, has shown bodyweight reduction and cardiometabolic benefits in adults with obesity across phase 3 trials globally. We aimed to assess the efficacy and safety of orforglipron versus placebo for treating obesity disease in Japanese adults. [METHODS] ATTAIN-J was a double-blind, randomised, placebo-controlled, parallel-group, phase 3 trial conducted across 16 medical research centres and hospitals in Japan and included adults aged 18 years or older with a BMI between 27 kg/m2 and less than 35 kg/m2 and two or more obesity-related health disorders, or a BMI of 35 kg/m2 or higher and one or more obesity-related health disorder, with one or more of the obesity-related health disorders being hypertension, dyslipidaemia, or type 2 diabetes (targeted at about 25% of participants), consistent with Japanese indications for tirzepatide and semaglutide for obesity disease; and at least one unsuccessful dietary attempt to lose weight. Participants were randomly assigned (1:1:1:1) via a computer-generated sequence to once-daily oral orforglipron (6 mg, 12 mg, or 36 mg) or placebo. Co-primary endpoints were mean percentage change in bodyweight and percentage of participants with at least 5% bodyweight reduction from baseline to week 72. Efficacy endpoints were primarily evaluated by the treatment regimen estimand in all randomly assigned participants. Safety was assessed in participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT05931380 (completed). [FINDINGS] Between July 31, 2023, and June 19, 2025, 291 participants were screened, of whom 238 (144 [61%] males and 94 [39%] females; mean age 54·1 years [SD 11·2]) were randomly assigned to receive orforglipron 6 mg (n=61), 12 mg (n=57), or 36 mg (n=60), or placebo (n=60); 214 (90%) participants completed the study. At week 72, mean percentage change in bodyweight was -5·9% (95% CI -7·6 to -4·2) with orforglipron 6 mg, -8·7% (-10·9 to -6·5) with 12 mg, and -7·9% (-10·0 to -5·8) with 36 mg, compared with -0·6% (-2·1 to 0·8) with placebo (all p<0·0001 vs placebo). At week 72, a bodyweight reduction of at least 5% was seen in 15·2% (SE 4·8; nine of 60) of participants in the placebo group compared with 45·6% (6·1; 28 of 61; p=0·0001) of participants in the orforglipron 6 mg group, 60·8% (6·4; 35 of 57; p<0·0001) of participants in the orforglipron 12 mg group, and 58·8% (6·5; 35 of 60; p<0·0001) of participants in the orforglipron 36 mg group. Adverse events with orforglipron were mostly mild-to-moderate gastrointestinal symptoms. Across all orforglipron groups, treatment-emergent adverse events that most frequently led to study treatment discontinuation were nausea (one [2%] of 61 in the 6 mg group, one [2%] of 57 in the 12 mg group, and five [8%] of 60 in the 36 mg group vs none with placebo) and vomiting (none in the 6 mg group, two [4%] in the 12 mg group, and one [2%] in the 36 mg group vs none in the placebo group). [INTERPRETATION] In Japanese adults with obesity disease, once-daily orforglipron resulted in statistically superior reductions in bodyweight versus placebo, with a safety profile consistent with that of other GLP-1 receptor agonists. [FUNDING] Eli Lilly and Company. [TRANSLATION] For the Japanese translation of the abstract see Supplementary Materials section.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Nov 1, 2026 | 42962687 first ingestion |
| owner-review | Nov 6, 2026 | reviewed_by set to Carrie Schluter (2026-11-05) on the owner's own confirmation. The assessment is unchanged and still the auto-classifier's, so its extracted values stay withheld under the 2026-10-18 decision. |
| reextract | Nov 6, 2026 | manufacturer: 'Eli Lilly, Lilly, Novo Nordisk, AstraZeneca, Sanofi, Boehringer Ingelheim, Amgen, Pfizer' -> 'Eli Lilly'; dose: '6 mg' -> '6 mg, 12 mg, 36 mg'. Q-043: manufacturer and drug_details.dose re-extracted by auto-classifier-v1.2. manufacturer no longer reads companies named only in the authors' conflicts statement (IN-062) and refuses a multi-company roster; dose is tied to the GLP-1 agent by name, never reads a concentration, and records a multi-dose design whole. Every other value is carried forward unchanged. Owner decision IN-064 option 1, 2026-11-06. |
| pubmed | Nov 8, 2026 | 42962687 duplicate matched on doi |