Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial
Authors' conclusion
In adults with obesity or overweight and type 2 diabetes, statistically superior reduction in bodyweight compared with placebo was demonstrated by once-daily orforglipron as an adjunct to lifestyle modification, with a safety profile similar to other GLP-1 receptor agonists.
Study context
- Population
- Adults with T2D and BMI ≥27 kg/m², HbA1c 7–10% (53–86 mmol/mol); baseline bodyweight 101.4 kg (SD 22.5), BMI 35.6 kg/m² (SD 6.6), HbA1c 8.05% (SD 0.75)1,444 completed
- Participants
- 1,613 adults
- Comparison
- Once-daily oral orforglipron 6 mg, 12 mg or 36 mg vs placebo, as adjunct to lifestyle modification
- Orforglipron 6 mgn = 329
- Orforglipron 12 mgn = 332
- Orforglipron 36 mgn = 322
- Placebon = 630reference
- Primary endpoint
- Mean percent change in bodyweight from baseline
- Follow-up
- Week 72
Methodological detailsphase 3, double-blind, placebo-controlled, multicentre, 136 sites in ten countries, 72-week trial; randomised 1:1:1:2 after dose-escalation phase
- Phase 3
- Double-blind
- Placebo-controlled
- Multicentre
- 136 sites in ten countries
- 72-week trial; randomised 1:1:1:2 after dose-escalation phase
Primary result
As reported in the abstract
Mean percent change in bodyweight · baseline to week 72
Orforglipron 6 mg
−5.1
mean · 95% CI −6.0–-4.2 · %
Orforglipron 12 mg
−7.0
mean · CI −7.8–-6.2 · %
Orforglipron 36 mg
−9.6
mean · CI −10.5–-8.7 · %
Placebo
−2.5
mean · CI −3.0–-1.9 · %
Each group vs placeboEstimated treatment difference (95% CI)P value
Orforglipron 6 mg
−2.7(−3.7 to −1.6)
P < 0.0001Orforglipron 12 mg
−4.5(−5.5 to −3.6)
P < 0.0001Orforglipron 36 mg
−7.1(−8.2 to −6.1)
P < 0.0001Further findings
Prespecified weight and cardiometabolic measures incl. HbA1c
- All statistically significantly improved with orforglipron
Deaths
- Total deaths
- 10
- Deaths with orforglipron
- 6
- Deaths with placebo
- 4
- All deaths deemed unrelated to treatment except one in placebo and one in 12 mg orforglipron (no treatment-related association reported for the latter)
Safety
- Treatment discontinuation due to AEs (mainly gastrointestinal) — Placebo
- 4.1%
- Treatment discontinuation due to AEs (mainly gastrointestinal) — Discontinuation due to AEs with orforglipron (range across doses)
- 6.1-9.9%
Adverse events
- Most common AEs with orforglipron: mild-to-moderate gastrointestinal events, mainly during dose escalation
Original publication
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. Published 20 November 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →