Eli Lilly and Company (NYSE: LLY) today announced positive topline Phase 3 results from ACHIEVE-1, evaluating the safety and efficacy of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. Orforglipron is the first oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist, taken without food and water restrictions, to successfully complete a Phase 3 trial. If approved, the company is confident in its ability to launch orforglipron worldwide without supply constraints. This would further Lilly's mission to reduce chronic diseases like type 2 diabetes, which is expected to impact an estimated 760 million adults by 2050.

礼来公司（纽约证券交易所代码：LLY）今日公布了ACHIEVE-1临床试验的积极关键数据，该试验评估了奥格列酮（Orforglipron）与安慰剂相比，在仅通过饮食和运动无法控制血糖的2型糖尿病成人患者中的安全性和有效性。奥格列酮是首个成功完成3期临床试验的口服小分子胰高血糖素样肽-1 ( GLP-1 ) 受体激动剂，无需限制饮食和饮水即可服用。如果获得批准，礼来公司有信心在全球范围内推出奥格列酮，且供应不受限制。这将进一步推进礼来公司减少2型糖尿病等慢性疾病的使命，预计到2050年，此类疾病将影响约7.6亿成年人。

"ACHIEVE-1 is the first of seven Phase 3 studies examining the safety and efficacy of orforglipron across people with diabetes and obesity. We are pleased to see that our latest incretin medicine meets our expectations for safety and tolerability, glucose control and weight loss, and we look forward to additional data readouts later this year," said David A. Ricks, Lilly chair and CEO. "As a convenient once-daily pill, orforglipron may provide a new option and, if approved, could be readily manufactured and launched at scale for use by people around the world."

“ACHIEVE-1 是七项 3 期临床试验中的第一项，旨在评估奥格列酮对糖尿病和肥胖症患者的安全性和有效性。我们很高兴看到，我们最新的肠促胰岛素药物在安全性和耐受性、血糖控制和减重方面均达到了我们的预期，我们期待在今年晚些时候获得更多数据。”戴维·A·里克斯礼来公司董事长兼首席执行官表示：“作为一种便捷的每日一次药片，奥格利普龙或许能提供一种新的治疗选择。如果获得批准，它可以轻松生产并大规模上市，供世界各地的人们使用。”

In the first Phase 3 trial of the ACHIEVE program, orforglipron met the primary endpoint of superior A1C reduction compared to placebo at 40 weeks, lowering A1C by an average of 1.3% to 1.6% from a baseline of 8.0%, using the efficacy estimand.2 In a key secondary endpoint, more than 65% of participants taking the highest dose of orforglipron achieved an A1C less than or equal to 6.5%, which is below the American Diabetes Association's (ADA) defined threshold for diabetes.3 In an additional key secondary endpoint, participants taking orforglipron lost an average of 16.0 lbs (7.9%) at the highest dose. Given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction was not yet attained.

在 ACHIEVE 项目的第一阶段 3 期临床试验中，奥格利普龙在 40 周时达到了与安慰剂相比更优的 A1C 降低效果的主要终点，使用疗效估计值，A1C 从基线的 8.0% 平均降低了 1.3% 至 1.6%。2在关键的次要终点中，超过 65% 服用最高剂量奥格利普龙的受试者的 A1C 低于或等于 6.5%，低于美国糖尿病协会(ADA) 定义的糖尿病阈值。3在另一个关键次要终点中，服用奥格列隆的受试者在最高剂量下平均减重 16.0 磅（7.9%）。鉴于受试者在研究结束时尚未达到体重平台期，因此似乎尚未达到完全减重。

For the treatment-regimen estimand,4 each dose of orforglipron led to statistically significant A1C reductions. In the key secondary endpoint for body weight, 12 mg and 36 mg doses led to statistically significant reductions. A1C reduction: 1.2% (3 mg), 1.5% (12 mg), 1.5% (36 mg), 0.4% (placebo) Percent weight reduction: 4.5% (3 mg), 5.8% (12 mg), 7.6% (36 mg), 1.7% (placebo) Weight reduction: 4.2 kg (9.3 lbs; 3 mg), 5.2 kg (11.5 lbs; 12 mg), 7.2 kg (15.8 lbs; 36 mg), 1.5 kg (3.4 lbs; placebo)

对于治疗方案估计目标，奥格列隆4个剂量组均显著降低了A1C。在关键次要终点——体重方面，12毫克和36毫克剂量组均显著降低了A1C。 A1C降低：1.2%（3毫克），1.5%（12毫克），1.5%（36毫克），0.4%（安慰剂） 体重减轻百分比：4.5%（3毫克）、5.8%（12毫克）、7.6%（36毫克）、1.7%（安慰剂） 体重减轻：4.2 公斤（9.3 磅；3 毫克）、5.2 公斤（11.5 磅；12 毫克）、7.2 公斤（15.8 磅；36 毫克）、1.5 公斤（3.4 磅；安慰剂）

The overall safety profile of orforglipron in ACHIEVE-1 was consistent with the established GLP-1 class. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity. The most common adverse events for participants treated with orforglipron (3 mg, 12 mg and 36 mg, respectively) were diarrhea (19%, 21% and 26%) vs. 9% with placebo, nausea (13%, 18% and 16%) vs. 2% with placebo, dyspepsia (10%, 20% and 15%) vs. 7% with placebo, constipation (8%, 17% and 14%) vs. 4% with placebo, and vomiting (5%, 7% and 14%) vs. 1% with placebo. Overall treatment discontinuation rates due to adverse events were 6% (3 mg), 4% (12 mg) and 8% (36 mg) for orforglipron vs. 1% with placebo. No hepatic safety signal was observed.

奥格利普隆在ACHIEVE-1试验中的总体安全性与已确定的GLP-1类药物一致。最常见的报告不良事件与胃肠道相关，严重程度通常为轻度至中度。奥格利普隆（3毫克、12毫克和36毫克）治疗组受试者最常见的不良事件包括腹泻（19%、21%和26%），安慰剂组为9%；恶心（13%、18%和16%），安慰剂组为2%；消化不良（10%、20%和15%），安慰剂组为7%；便秘（8%、17%和14%），安慰剂组为4%；呕吐（5%、7%和14%），安慰剂组为1%。奥格列隆组因不良事件导致的总体治疗终止率分别为6%（3毫克）、4%（12毫克）和8%（36毫克），安慰剂组为1%。未观察到肝脏安全性信号。

The ACHIEVE-1 results will be presented at ADA's 85th Scientific Sessions and published in a peer-reviewed journal. More results from the ACHIEVE Phase 3 clinical trial program will be shared later this year, along with findings from the ATTAIN Phase 3 clinical trial program evaluating orforglipron for weight management. Lilly expects to submit orforglipron for weight management to global regulatory agencies by the end of this year, with the submission for the treatment of type 2 diabetes anticipated in 2026.

ACHIEVE-1 的结果将在茴香在第85届科学会议上，该研究成果发表在同行评审期刊上。ACHIEVE 3期临床试验项目的更多结果将于今年晚些时候公布，同时还将公布ATTAIN 3期临床试验项目的结果，该项目旨在评估奥格列酮在体重管理中的应用。礼来公司预计将于今年年底前向全球监管机构提交奥格列酮用于体重管理的申请，并预计于2026年提交其用于治疗2型糖尿病的申请。