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.

This study aimed to assess orforglipron as add-on treatment to diet and exercise alone or to oral antihyperglycaemic medications in Japanese participants with type 2 diabetes.

本研究旨在评估Orforglipron作为饮食和运动疗法或口服降糖药物的辅助治疗，在日本2型糖尿病患者中的效果。

Methods

This multicentre, randomised, open-label phase 3 study was conducted in 40 medical research centres and hospitals in Japan.

这项多中心、随机、开放标签的3期研究在日本的40个医疗研究中心和医院进行。

Adults with type 2 diabetes and elevated glucose levels managing their condition with diet and exercise alone or with one or two oral antihyperglycaemic medications were assigned (1:1:1) via computer-generated random sequence to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg).

成年2型糖尿病患者，通过饮食和运动或一种或两种口服降糖药物控制血糖水平，通过计算机生成的随机序列（1:1:1）被分配接受每日一次口服Orforglipron（3 mg, 12 mg或36 mg）。

Randomisation was stratified by background therapy, baseline HbA1c (≤8·5% or >8·5%), and metformin use (yes vs no; applied only to α-glucosidase inhibitors, thiazolidinedione, and glinides).

随机分组根据背景治疗、基线HbA1c（≤8·5%或>8·5%）和二甲双胍使用情况（是与否；仅适用于α-葡萄糖苷酶抑制剂、噻唑烷二酮和格列奈类药物）进行分层。

Investigators, participants, and site staff were not masked to treatment.

研究者、参与者和现场工作人员未对治疗进行盲法处理。

The primary endpoint was safety for 52 weeks, assessed in all randomly assigned participants who received at least one dose of orforglipron.

主要终点是安全性，评估所有至少接受一次Orforglipron剂量的随机分配参与者，为期52周。

This study is registered with ClinicalTrials.gov, NCT06010004 (ACHIEVE-J).

这项研究已在ClinicalTrials.gov注册，注册号为NCT06010004（ACHIEVE-J）。

Results

Between Sept 28, 2023, and June 5, 2025, 450 participants were screened and 401 were randomly assigned to three groups (3 mg, n=132; 12 mg, n=135; and 36 mg, n=134). 352 (88%) completed study treatment. 339 participants (85%, 95% CI 80·7-87·8) had at least one treatment-emergent adverse event(TEAE), more frequently in the 36-mg group (118 [88%, 95% CI 81·5-92·5]) than in the 3-mg (107 [81%, 73·5-86·8]) and 12-mg (114 [84%, 77·4-89·6]) groups.

在2023年9月28日至2025年6月5日期间，共有450名参与者接受了筛选，其中401名被随机分配到三个组别（3毫克组，n=132；12毫克组，n=135；36毫克组，n=134）。352名（88%）完成了研究治疗。339名参与者（85%，95% CI 80·7-87·8）至少出现了一次治疗后不良事件（TEAE），其中36毫克组（118 [88%，95% CI 81·5-92·5]）的发生率高于3毫克组（107 [81%，73·5-86·8]）和12毫克组（114 [84%，77·4-89·6]）。

Most TEAEs were of mild (267 [67%, 61·8-71·0]) or moderate (63 [16%, 12·5-19·6]) severity.

大多数TEAEs为轻度（267 [67%，61·8-71·0]）或中度（63 [16%，12·5-19·6]）严重程度。

Discontinuations due to an adverse eventoccurred in 19 of 134 participants (14%, 95% CI 9·3-21·1) in the 36-mg group compared with seven of 132 (5%, 2·6-10·5) in the 3-mg group and 11 of 135 (8%, 4·6-14·0) in the 12-mg group.

由于不良事件导致的停药情况，在36毫克组的134名参与者中有19人（14%，95% CI 9·3-21·1），而在3毫克组的132人中有7人（5%，2·6-10·5），12毫克组的135人中有11人（8%，4·6-14·0）。

Across treatment groups, gastrointestinal symptoms were the most common TEAEs leading to study treatment discontinuation (3 mg: 5 [3·8%, 1·6-8·6]; 12 mg: 8 [5·9%, 3·0-11·3]; and 36 mg: 11 [8·2%, 4·7-14·1]).

在各治疗组中，胃肠道症状是导致研究治疗中断的最常见TEAEs（3毫克组：5 [3·8%，1·6-8·6]；12毫克组：8 [5·9%，3·0-11·3]；36毫克组：11 [8·2%，4·7-14·1]）。

Level 2 (blood glucose <54 mg/dL) hypoglycaemia events occurred in three of 135 participants in the 12-mg group (2%, 0·8-6·3) and in three of 134 in the 36-mg group (2%, 0·8-6·4) groups.

在12毫克组的135名参与者中有3人（2%，0·8-6·3）和在36毫克组的134人中有3人（2%，0·8-6·4）发生了2级（血糖<54 mg/dL）低血糖事件。

No level 3 (severe) hypoglycaemia events occurred.

没有发生3级（严重）低血糖事件。

Outcomes were generally similar across background therapies.

在不同基础治疗中，结果大致相似。

interpretation

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.

在为期52周的研究中，使用orforglipron结合饮食和运动，或与一种或两种口服降糖药物联合使用，对日本成年2型糖尿病患者显示出可接受的安全性。

funding

Eli Lilly.

礼来公司。

translation

For the Japanese translation of the abstract see Supplementary Materials section.

摘要的日文翻译请参见补充材料部分。