General information with sources. Never a substitute for your doctor.

MethodologyAbout the authorESEN
SaciedadSearch

Randomized controlled trial

ACHIEVE-J: long-term safety of orforglipron in Japanese adults

Over 52 weeks, 85% of participants had at least one adverse event (81%, 84% and 88% on 3, 12 and 36 mg), mostly mild (67%) or moderate (16%).

Yabe D et al. 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. The Lancet Diabetes & Endocrinology, 2026. DOI: 10.1016/S2213-8587(26)00138-5

Prepared by
Last updated
Next review
Sources
3 sources

No clinical review. No advertising from drug companies and no affiliate links.How we work

Key facts

Drug
orforglipron
Design
Randomized controlled trial
Participants
401
Duration
52 weeks
Funding
Eli Lilly
Registry
NCT06010004
Population
401 Japanese adults with type 2 diabetes managed with diet and exercise alone or with one or two oral glucose-lowering drugs, at 40 centers in Japan.
Primary outcome
Safety over 52 weeks (adverse events) with oral orforglipron 3, 12 or 36 mg daily, randomly assigned and open-label, with no placebo or comparator group.

What it found

Over 52 weeks, 85% of participants had at least one adverse event (81%, 84% and 88% on 3, 12 and 36 mg), mostly mild (67%) or moderate (16%). Discontinuations because of adverse events occurred in 5%, 8% and 14% on 3, 12 and 36 mg, mostly because of digestive symptoms (3.8%, 5.9% and 8.2%). Level 2 hypoglycemia (glucose below 54 mg/dL) occurred in 3 participants on 12 mg and 3 on 36 mg (2% in each group), and there was no severe hypoglycemia. Of the 401 participants, 352 (88%) completed study treatment.

Limitations

Funded by Eli Lilly, the maker of orforglipron. Open-label design with no placebo or comparator group, so it cannot show how much of the adverse events is due to the drug. It only included Japanese people, with a safety rather than an efficacy goal. The published abstract does not give the changes in HbA1c or weight.

What it means for you

In Japanese adults with type 2 diabetes, orforglipron tablets caused mainly digestive side effects over one year, more often at the highest dose, and no severe hypoglycemia. There was no placebo or comparator group, so it does not say how the drug compares with other treatments or how much it lowers blood sugar. Your doctor can tell you whether it is authorized where you live and whether it makes sense for your treatment.

Further reading

Related trials

  • orforglipron40 weeks

    ACHIEVE-2

    At 40 weeks, HbA1c fell by 1.23, 1.50 and 1.56 points with orforglipron 3, 12 and 36 mg, compared with 0.81 on dapagliflozin.

  • orforglipron and semaglutide52 weeks

    ACHIEVE-3

    HbA1c fell by 1.71 and 1.91 points with orforglipron 12 and 36 mg, and by 1.23 and 1.47 points with oral semaglutide 7 and 14 mg.

  • orforglipron40 weeks

    ACHIEVE-5

    At 40 weeks, HbA1c fell by 1.58, 1.88 and 1.82 points with orforglipron 3, 12 and 36 mg, compared with 0.79 on placebo.

  • orforglipron40 weeks

    ACHIEVE-1

    HbA1c fell by 1.24, 1.47 and 1.48 percentage points with orforglipron 3, 12 and 36 mg, compared with 0.41 points on placebo.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. The Lancet Diabetes & Endocrinology.Yabe D, et al. Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J). Lancet Diabetes Endocrinol. 2026;14(10):841-855.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 42607698 (abstract).accessed .
  3. ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT06010004 (ACHIEVE-J: registration).accessed .