Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial
Authors' conclusion
Treatment with orforglipron in combination with diet and exercise alone or one or two oral antihyperglycaemic medications for 52 weeks demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes.
Study context
- Population
- Japanese adults with T2D and elevated glucose managed with diet and exercise alone or with one or two oral antihyperglycaemic medications; 40 centres in Japan352 completed treatment
- Participants
- 401 adults
- Comparison
- Once-daily oral orforglipron 3 mg vs 12 mg vs 36 mg
- 3 mgn = 132
- 12 mgn = 135
- 36 mgn = 134
- Primary endpoint
- Safety, in all randomised participants who received ≥1 dose of orforglipron
- Follow-up
- 52 weeks
Methodological detailsmulticentre, open-label, parallel-group, phase 3, Randomised 1:1:1, stratified by background therapy, baseline HbA1c (≤8.5% or >8.5%) and metformin use
- Multicentre
- Open-label
- Parallel-group
- Phase 3
- Randomised 1:1:1, stratified by background therapy, baseline HbA1c (≤8.5% or >8.5%) and metformin use
Primary result
As reported in the abstract
≥1 treatment-emergent adverse event (TEAE)
- Overall ≥1 treatment-emergent adverse event (TEAE)
- 339 (85%, 95% CI 80.7-87.8)
- Mild TEAEs
- 267 (67%, 61.8-71.0)
- Moderate TEAEs
- 63 (16%, 12.5-19.6)
Further findings
- Outcomes were generally similar across background therapies
Safety
| Outcome | 3 mg | 12 mg | 36 mg |
|---|---|---|---|
| ≥1 TEAE · 52 weeks | 81% (CI 73.5–86.8) | 84% (CI 77.4–89.6) | 88% (CI 81.5–92.5) |
| Discontinuation due to AE | 5% (CI 2.6–10.5) | 8% (CI 4.6–14.0) | 14% (CI 9.3–21.1) |
| GI symptoms leading to treatment discontinuation | 3.8% (CI 1.6–8.6) | 5.9% (CI 3.0–11.3) | 8.2% (CI 4.7–14.1) |
| Hypoglycaemia | — not stated in the abstract | 2% (CI 0.8–6.3) | 2% (CI 0.8–6.4) |
— not stated in the abstract
- ≥1 TEAE — Overall ≥1 TEAE
- 339 (85%, 95% CI 80.7-87.8)
- Hypoglycaemia: level 2 (blood glucose <54 mg/dL)
TEAE severity
- Mild
- 267 [67%, 61.8-71.0]
- Moderate
- 63 [16%, 12.5-19.6]
Hypoglycaemia
- No level 3 (severe) hypoglycaemia events occurred
Original publication
Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial. Lancet Diabetes Endocrinol. Published 17 August 2026. doi:10.
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