Efficacy and safety of orforglipron in adults with body mass index of 27 to less than 30 kg/m2 and adiposity-related complications: A post hoc analysis of the ATTAIN-1 trial
- Design
- Randomized trial · 260 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all 260 participants had BMI ≥27 to <30 kg/m2 with at least one adiposity-related complication, and the parent trial enrolled adults without diabetes; no age data are reported.
- Could weight loss explain it?
- Not applicablenot_applicable: the headline outcome is percent change in body weight, with BMI, categorical weight loss and waist circumference alongside it, so whether weight loss explains the result is not a question (IN-062). The lipid and patient-reported improvements were reported next to a -13.5% weight reduction and were not separated from it, so no independent mediation claim is made for them.
- Study tier
- Study tier 3LOW: a post hoc subgroup analysis of 260 of the randomised participants in one double-blind, placebo-controlled phase 3 trial. Randomisation and blinding are strong, but the subset was not prespecified, the p value is described as nominal, no confidence intervals are given, and the endpoints are weight, anthropometry, lipids and patient-reported outcomes rather than clinical events.
- Assessment
- Version 4 · 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.
This is a post hoc analysis of 260 participants from the randomised, double-blind, placebo-controlled ATTAIN-1 trial who had a BMI ≥27 to <30 kg/m2 with at least one adiposity-related complication and who did not have diabetes. At Week 72, once-daily oral orforglipron 17.2 mg was associated with a mean body weight reduction of -13.5% against -0.3% on placebo (nominal p < 0.001), with improvements in waist circumference, triglycerides, low-density lipoprotein cholesterol and patient-reported outcomes; females reduced body weight by up to -18.8% and males by up to -10.0%. Safety was described as consistent with previous trials, predominantly mild-to-moderate gastrointestinal events. The subgroup was not prespecified and no confidence intervals are reported.
01Findings
What the study reported
- Drugs
- Orforglipron
- Dose
- 5.5, 9, or 17.2 mg once daily
- Treatment duration
- 72 weeks
- Comparator
- placebo
- Route
- oral
- Primary outcome
- percent change in body weight from baseline to Week 72
- Effect
- At Week 72 mean percent body weight reduction was -13.5% with orforglipron 17.2 mg versus -0.3% with placebo (nominal p < 0.001); females reduced body weight by up to -18.8% and males by up to -10.0%; waist circumference, triglycerides, low-density lipoprotein cholesterol and patient-reported outcomes also improved.
- 95% confidence interval
- not reported in abstract
- P value
- nominal p < 0.001
- Follow-up
- 72 weeks
- Adverse events
- safety profile consistent with previous trials, with predominantly mild-to-moderate gastrointestinal events
- Limitations
- A post hoc, not prespecified, subgroup analysis of one phase 3 trial: 260 participants across four groups, p values described as nominal, no confidence intervals, and endpoints limited to weight, anthropometry, lipids and patient-reported outcomes over 72 weeks.
Who was studied
- Bmi min
- 27
- Obesity status
- excluded (the subset is restricted to BMI ≥27 to <30 kg/m2, described as overweight)
- Diabetes status
- excluded
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- overweight (BMI ≥27 to <30 kg/m2) with at least one adiposity-related complication, without diabetes
- Sample size
- 260
- Inclusion exclusion
- adults without diabetes with obesity or overweight in the parent trial; this analysis restricted to BMI ≥27 to <30 kg/m2 with at least one adiposity-related complication
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 260
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 72 weeks
- Outcome type
- intermediate
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- no CI reported; nominal p < 0.001 for the weight endpoint; 260 participants across four groups (56, 64, 62 and 78)
- Risk of bias
- not assessed
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- Three academic authors report consulting fees, research funding, honoraria or shareholdings from many pharmaceutical companies including Eli Lilly and Novo Nordisk, and six authors are employees and shareholders of Eli Lilly and Company.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly and Company; six authors are its employees and shareholders and others report its consulting fees, honoraria or research funding.
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Orforglipron, an oral small-molecule glucagon-like peptide-1 receptor agonist, improved body weight and cardiometabolic parameters in the phase 3 ATTAIN-1 trial, but its efficacy and safety in adults with body mass index (BMI) of ≥27 to <30 kg/m2 and adiposity-related complications have not been characterized. Adults with overweight and an adiposity-related complication are at substantial cardiometabolic risk, and obesity medications are recommended for this group. [METHODS] This was a post-hoc analysis of the ATTAIN-1 trial (NCT05869903), a phase 3, randomized, double-blind, placebo-controlled trial in which adults without diabetes and with obesity or overweight were randomized 3:3:3:4 to once-daily oral orforglipron 5.5, 9, or 17.2 mg or placebo for 72 weeks. The present analysis included the subset of randomized participants with BMI ≥27 to <30 kg/m2 and ≥1 adiposity-related complication. Endpoints included change from baseline to Week 72 the percent change in body weight, BMI, categorical weight-loss, waist circumference, lipids, patient-reported outcomes, and safety. Effect estimates are reported using efficacy and treatment-regimen estimands. Efficacy endpoints were also reported per sex subgroup. [RESULTS] This analysis included 260 participants (orforglipron 5.5 mg: 56; 9 mg: 64; 17.2 mg: 62; placebo: 78). At Week 72, orforglipron was associated with greater mean percent body weight reduction (17.2 mg: -13.5%) versus placebo (-0.3%) (nominal p < 0.001). Females experienced up to -18.8% mean body weight reduction and males up to -10.0%. Orforglipron was associated with improvements in waist circumference, triglycerides, and low-density lipoprotein cholesterol, as well as improvements in patient-reported outcomes. Safety profile was consistent with previous trials with predominantly mild-to-moderate gastrointestinal events. [CONCLUSION] In this post hoc analysis of ATTAIN-1, participants with BMI ≥27 to <30 kg/m2 and ≥1 adiposity-related complication, orforglipron was associated with improvements in anthropometric and cardiometabolic parameters, with a safety profile broadly consistent with the overall ATTAIN-1 trial (ClinicalTrials.gov identifier: NCT05869903).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Nov 1, 2026 | 42936354 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: 'Novo Nordisk, Eli Lilly, Lilly, AstraZeneca, Sanofi, Boehringer Ingelheim, Amgen, Pfizer' -> 'Eli Lilly'; dose: '17.2 mg' -> '5.5 mg, 9 mg, 17.2 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. |
| reextract | Nov 6, 2026 | industry_funded: 'unclear' -> 'yes'; sponsor_role: 'not reported in abstract' -> 'manufacturer funded the study (sponsor role in design/analysis not stated in abstract)'; funding_source: 'not reported in abstract' -> 'Eli Lilly (named in the conflicts statement)'; evidence_components.funding_conflicts: 'unclear' -> 'yes'. Q-043: manufacturer, drug_details.dose and the funding fields 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, records a multi-dose design whole and keeps a frequency written beside the amount; industry_funded, sponsor_role and funding_source read the conflicts statement's own sponsor sentences, a supplier counting as partial. Every other value is carried forward unchanged, evidence_level included. Owner decisions IN-064, 2026-11-06. |
| pubmed | Nov 8, 2026 | 42936354 duplicate matched on doi |