ACHIEVE-J: 52-Week Safety Data for Oral Orforglipron in Japanese Adults With Type 2 Diabetes Published in The Lancet Diabetes & Endocrinology

The Lancet Diabetes & Endocrinology published results on August 17, 2026 from ACHIEVE-J, a phase 3 trial evaluating the long-term safety of the oral GLP-1 receptor agonist orforglipron in Japanese adults with type 2 diabetes. The multicentre, randomised, open-label trial was conducted at 40 medical research centres and hospitals in Japan and was funded by Eli Lilly and Company, which developed the drug. The corresponding author was Masakazu Takeuchi of Eli Lilly Japan.

Orforglipron is a non-peptide small molecule that activates the GLP-1 receptor and is taken as a once-daily tablet. The FDA approved it in 2026 under the brand name Foundayo for chronic weight management in adults with obesity, or overweight with weight-related conditions. It does not currently hold FDA approval for type 2 diabetes. ACHIEVE-J is registered on ClinicalTrials.gov as NCT06010004 and is one of several trials in Eli Lilly's ACHIEVE program studying orforglipron in that indication.

Between September 28, 2023 and June 5, 2025, investigators screened 450 participants and randomly assigned 401 adults with type 2 diabetes, managing their condition through diet and exercise alone or with one or two oral antihyperglycaemic medications, to once-daily oral orforglipron at 3 mg (132 participants), 12 mg (135 participants) or 36 mg (134 participants) for 52 weeks. The trial had no placebo or active comparator arm; all three groups received orforglipron at different doses.

Overall, 352 participants (88%) completed study treatment. Treatment-emergent adverse events occurred in 339 participants (85%), more frequently in the 36 mg group (88%) than the 3 mg (81%) or 12 mg (84%) groups. Most were mild or moderate in severity, and gastrointestinal symptoms were the most common adverse events leading to discontinuation. Discontinuations due to an adverse event occurred in 14% of the 36 mg group, compared with 8% at 12 mg and 5% at 3 mg. Level 2 hypoglycemia, defined as blood glucose below 54 mg/dL, occurred in about 2% of participants in the 12 mg and 36 mg groups; no level 3 (severe) hypoglycemia was reported at any dose.

The study authors concluded that orforglipron, combined with diet and exercise alone or with one or two oral antihyperglycaemic medications over 52 weeks, demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes, with outcomes generally consistent across background therapies. The trial measured safety and tolerability as its focus rather than glycemic or weight-loss efficacy, and it followed ACHIEVE-2, a separate global phase 3 trial published in July 2026 that compared orforglipron with the SGLT2 inhibitor dapagliflozin on blood sugar control.

As a single-arm-by-dose safety study without a placebo group, ACHIEVE-J does not by itself establish a type 2 diabetes indication for orforglipron, and the reported adverse-event rates describe this specific 401-person Japanese trial population rather than a general prediction for all patients. Orforglipron remains approved in the United States only for chronic weight management as of this trial's publication, and this report describes trial findings rather than treatment or dosing guidance.