Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial
Authors' conclusion
Orforglipron demonstrated superior glycaemic control compared with dapagliflozin, with a tolerability profile consistent with the GLP-1 receptor agonist class, including increased rates of discontinuation due to adverse events
Study context
- Population
- Adults with T2D on metformin (≥1500 mg/day), HbA1c 7.0%–10.5% (53–91 mmol/mol), stable bodyweight (±5%), BMI ≥23.0 kg/m²; 73 sites in six countries; mean age 56.1 years, 49% femalerandomised 1:1:1:1
- Participants
- 962 adults
- Comparison
- Once-daily oral orforglipron vs dapagliflozin 10 mg
- Orforglipron 3 mgn = 240
- Orforglipron 12 mgn = 241
- Orforglipron 36 mgn = 241
- Dapagliflozin 10 mgn = 240reference
- Primary endpoint
- Change from baseline in HbA1c (non-inferiority margin 0.3% vs dapagliflozin)
- Follow-up
- Week 40
Methodological detailsphase 3, multicentre, open-label (orforglipron dose-blinded), non-inferiority
- Phase 3
- Multicentre
- Open-label (orforglipron dose-blinded)
- Non-inferiority
Primary result
As reported in the abstract
Change from baseline in mean HbA1c
Orforglipron 3 mg
−1.23
mean · SE 0.08 · %
Orforglipron 12 mg
−1.50
mean · SE 0.08 · %
Orforglipron 36 mg
−1.56
mean · SE 0.09 · %
Dapagliflozin 10 mg
−0.81
mean · SE 0.07 · %
Each group vs dapagliflozin 10 mgEstimated treatment difference, % (95% CI)P value
Orforglipron 3 mg
−0.42(−0.62 to −0.23)
P < 0.0001Orforglipron 12 mg
−0.70(−0.90 to −0.49)
P < 0.0001Orforglipron 36 mg
−0.75(−0.96 to −0.55)
P < 0.0001Non-inferiority margin 0.3 as printed, not drawn
Safety
Mild-to-moderate gastrointestinal adverse events
Study intervention discontinuations
Severe hypoglycaemia
- No severe episode of hypoglycaemia was reported
Original publication
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. Lancet. Published 8 June 2026. doi:10.
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