Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the Phase 3 ATTAIN-1 trial, evaluating orforglipron, an investigational oral glucagon-like peptide-1 (GLP-1) receptor agonist, in 3,127 adults with obesity, or overweight with a weight-related medical problem and without diabetes. At 72 weeks, all three doses of orforglipron, met the primary endpoint and all key secondary endpoints compared to placebo, delivering clinically meaningful weight loss as an adjunct to a healthy diet and physical activity. For the primary endpoint, orforglipron 36 mg, taken once per day without food and water restrictions, lowered weight by an average of 12.4% (27.3 lbs) compared to 0.9% (2.2 lbs) with placebo using the efficacy estimand.

礼来公司（纽约证券交易所代码：LLY）今天宣布了 3 期 ATTAIN-1 试验的积极顶线结果，该试验评估了 orforglipron，一种研究性口服胰高血糖素样肽-1 （GLP-1） 受体激动剂，用于 3,127 名肥胖或超重且没有糖尿病的成年人。在72周时，与安慰剂相比，所有三剂奥格列普隆均达到主要终点和所有关键次要终点，作为健康饮食和身体活动的辅助手段，提供了具有临床意义的减肥效果。对于主要终点，或福格列普隆 36 毫克，每天服用一次，不受食物和水限制，与使用疗效估计的安慰剂组相比，体重平均降低了 12.4%（27.3 磅），而安慰剂组的体重降低了 0.9%（2.2 磅）。

"Obesity is one of the most pressing global health challenges of our time, driving global chronic disease burden and impacting more than one billion people worldwide," said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. "With orforglipron, we're working to transform obesity care by introducing a potential once-daily oral therapy that could support early intervention and long-term disease management, while offering a convenient alternative to injectable treatments. With these positive data in hand, we are now planning to submit orforglipron for regulatory review by year-end and are prepared for a global launch to address this urgent public health need."

“肥胖是我们这个时代最紧迫的全球健康挑战之一，它推动了全球慢性病负担并影响着全球超过 10 亿人，”礼来公司执行副总裁兼总裁肯尼思·卡斯特博士说。“通过奥格列普隆，我们正在努力通过引入一种潜在的每日一次口服疗法来改变肥胖护理，该疗法可以支持早期干预和长期疾病管理，同时提供注射治疗的便捷替代方案。有了这些积极的数据，我们现在计划在年底前将奥格列普隆提交监管审查，并准备在全球推出，以满足这一紧迫的公共卫生需求。

In the ATTAIN-1 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo. Participants taking the highest dose of orforglipron lost an average of 27.3 lbs (12.4%) at 72 weeks using the efficacy estimand. In a key secondary endpoint, 59.6% of participants taking the highest dose of orforglipron lost at least 10% of their body weight, while 39.6% lost at least 15% of their body weight. In addition to achieving significant weight loss, orforglipron was also associated with reductions in known markers of cardiovascular risk, including non-HDL cholesterol, triglycerides and systolic blood pressure in pooled analyses across all doses. In a pre-specified exploratory analysis, the highest dose of orforglipron reduced high-sensitivity C-reactive protein (hsCRP) levels by 47.7%.

在 ATTAIN-1 试验中，与安慰剂相比，奥格列酮达到了优异的体重减轻的主要终点。使用疗效估计，服用最高剂量奥格列酮的参与者在 72 周时平均减重 27.3 磅 （12.4%）。在一个关键的次要终点中，服用最高剂量奥格列普隆的参与者中有 59.6% 的体重减轻了至少 10%，而 39.6% 的参与者减轻了至少 15% 的体重。除了实现显着的体重减轻外，在所有剂量的汇总分析中，奥格列普隆还与已知心血管风险标志物的降低有关，包括非高密度脂蛋白胆固醇、甘油三酯和收缩压。在预先指定的探索性分析中，最高剂量的奥格列普隆可将高敏 C 反应蛋白 （hsCRP） 水平降低 47.7%。

For the treatment-regimen estimand,2 each dose of orforglipron led to statistically significant improvements across the primary and all key secondary endpoints. Percent weight reduction: -7.5% (-7.8 kg; 17.2 lbs; 6 mg), -8.4% (-8.6 kg; 19.0 lbs; 12 mg), -11.2% (-11.3 kg; 25.0 lbs; 36 mg), -2.1% (-2.4 kg; 5.3 lbs; placebo) Percentage of participants achieving body weight reductions of ≥10%: 33.3% (6 mg), 40.0% (12 mg), 54.6% (36 mg), 12.9% (placebo) Percentage of participants achieving body weight reductions of ≥15%: 15.1% (6 mg), 20.3% (12 mg), 36.0% (36 mg), 5.9% (placebo)

对于治疗方案估计，2每一剂奥格列普隆在主要终点和所有关键次要终点方面都有统计学上的显着改善。 体重减轻百分比：-7.5%（-7.8 kg;17.2 lbs;6 mg）、-8.4%（-8.6 kg、19.0 lbs、12 mg）、-11.2%（-11.3 kg、25.0 lbs、36 mg）、-2.1%（-2.4 kg;5.3 lbs;安慰剂） 体重减轻 ≥10% 的参与者百分比：33.3%（6 毫克）、40.0%（12 毫克）、54.6%（36 毫克）、12.9%（安慰剂） 体重减轻 ≥15% 的参与者百分比：15.1%（6 毫克）、20.3%（12 毫克）、36.0%（36 毫克）、5.9%（安慰剂）

The overall safety profile of orforglipron in ATTAIN-1 was consistent with the established GLP-1 receptor agonist 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 (6 mg, 12 mg and 36 mg, respectively) were nausea (28.9%, 35.9% and 33.7%) vs. 10.4% with placebo, constipation (21.7%, 29.8% and 25.4%) vs. 9.3% with placebo, diarrhea (21.0%, 22.8% and 23.1%) vs. 9.6% with placebo, vomiting (13.0%, 21.4% and 24.0%) vs. 3.5% with placebo, and dyspepsia (13.0%, 16.2% and 14.1%) vs. 5.0% with placebo. Treatment discontinuation rates due to adverse events were 5.1% (6 mg), 7.7% (12 mg) and 10.3% (36 mg) for orforglipron vs. 2.6% with placebo. The overall treatment discontinuation rates were 21.9% (6 mg), 22.5% (12 mg) and 24.4% (36 mg) for orforglipron vs. 29.9% with placebo. No hepatic safety signal was observed.

奥格列普隆在 ATTAIN-1 中的总体安全性与已建立的 GLP-1 受体激动剂类别一致。最常报告的不良事件是胃肠道相关，严重程度通常为轻度至中度。接受奥格列普隆（分别为6mg、12mg和36mg）治疗的受试者最常见的不良事件是恶心（28.9%、35.9%和33.7%）与安慰剂组的10.4%、便秘（21.7%、29.8%和25.4%）与安慰剂组的9.3%、腹泻（21.0%、22.8%和23.1%）与安慰剂组的9.6%、呕吐（13.0%、21.4%和24.0%）与安慰剂组的3.5%以及消化不良（13.0%， 16.2% 和 14.1%），安慰剂组为 5.0%。奥格列普隆因不良事件导致的治疗中断率分别为5.1%（6mg）、7.7%（12mg）和10.3%（36mg），而安慰剂组为2.6%。奥格列普隆的总体治疗中止率分别为21.9%（6毫克）、22.5%（12毫克）和24.4%（36毫克），而安慰剂组为29.9%。未观察到肝脏安全信号。

The detailed ATTAIN-1 results will be presented next month at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025 and published in a peer-reviewed journal. More results from the ATTAIN Phase 3 clinical trial program will be shared later this year, along with findings from the ACHIEVE Phase 3 clinical trial program evaluating orforglipron for adults with type 2 diabetes.

详细的 ATTAIN-1 结果将于下个月在欧洲糖尿病研究协会 （EASD） 2025 年年会上公布，并发表在同行评审期刊上。ATTAIN 3 期临床试验计划的更多结果将于今年晚些时候分享，以及评估 orforglipron 治疗成人 2 型糖尿病的 ACHIEVE 3 期临床试验计划的结果。

About orforglipron Orforglipron (or-for-GLIP-ron) is an investigational, once-daily small molecule (non-peptide) oral glucagon-like peptide-1 receptor agonist that can be taken any time of the day without restrictions on food and water intake.3 Orforglipron was discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018. Chugai and Lilly published the preclinical pharmacology data of this molecule together.4 Lilly is running Phase 3 studies on orforglipron for the treatment of type 2 diabetes and for weight management in adults with obesity or overweight with at least one weight-related medical problem. It is also being studied as a potential treatment for obstructive sleep apnea (OSA) and hypertension in adults with obesity.

关于 orforglipronOrforglipron （or-for-GLIP-ron） 是一种研究性、每日一次的小分子（非肽）口服胰高血糖素样肽-1 受体激动剂，可以在一天中的任何时间服用，不受食物和水的摄入限制。3Orforglipron 由中外制药株式会社发现，并于 2018 年获得礼来公司许可。中外制药和礼来共同发表了该分子的临床前药理学数据。4礼来公司正在进行奥格列普隆的 3 期研究，用于治疗 2 型糖尿病，并用于肥胖或超重且至少有一种体重相关医疗问题的成年人的体重管理。它还被研究作为成人肥胖症阻塞性睡眠呼吸暂停 （OSA） 和高血压的潜在治疗方法。

About ATTAIN-1 and ATTAIN clinical trial program ATTAIN-1 (NCT05869903) is a Phase 3, 72-week, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of orforglipron 6 mg, 12 mg and 36 mg as monotherapy to placebo in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, OSA or cardiovascular disease, who did not have diabetes. The trial randomized 3,127 participants across the U.S., Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain and Taiwan in 3:3:3:4 ratio to receive either 6 mg, 12 mg or 36 mg orforglipron or placebo. The primary objective of the study was to demonstrate that orforglipron (6 mg, 12 mg, 36 mg) is superior to placebo in body weight reduction from baseline after 72 weeks in people with a BMI ≥30.0 kg/m² or a BMI ≥27.0 kg/m² with at least one weight-related comorbidity and a history of at least one self-reported unsuccessful dietary effort to lose body weight. All participants in the orforglipron treatment arms started the study at a dose of orforglipron 1 mg once-daily and then increased the dose in a step-wise approach at four-week intervals to their final randomized maintenance dose of 6 mg (via steps at 1 mg and 3 mg), 12 mg (via steps at 1 mg, 3 mg and 6 mg) or 36 mg (via steps at 1 mg, 3 mg, 6 mg, 12 mg and 24 mg). Dose reduction was only allowed for GI tolerability if other mitigations failed.

关于 ATTAIN-1 和 ATTAIN 临床试验计划 ATTAIN-1 （NCT05869903） 是一项为期 72 周的 3 期、为期 72 周、随机、双盲、安慰剂对照试验，比较奥格列普隆 6 毫克、12 毫克和 36 毫克作为单一疗法与安慰剂在肥胖或超重并伴至少一种以下合并症的成人中的疗效和安全性：高血压、血脂异常、OSA 或心血管疾病， 谁没有糖尿病。该试验以 3：3：3：4 的比例随机分配了来自美国、巴西、中国、印度、日本、韩国、波多黎各、斯洛伐克、西班牙和台湾的 3,127 名参与者，分别接受 6 毫克、12 毫克或 36 毫克或福格列普隆或安慰剂。该研究的主要目的是证明奥格列普隆（6 mg、12 mg、36 mg）在 BMI ≥30.0 kg/m² 或 BMI ≥27.0 kg/m² 的人群中，在 72 周后体重较基线减轻方面优于安慰剂，并且至少有一次自我报告的减肥不成功饮食努力史。orforglipron 治疗组的所有参与者都以 orforglipron 1 mg 的剂量开始研究，每天一次，然后以 4 周的间隔逐步增加剂量，达到他们的最终随机维持剂量为 6 mg（通过 1 mg 和 3 mg 的步骤）、12 mg（通过 1 mg、3 mg 和 6 mg 的步骤）或 36 mg（通过 1 mg 的步骤， 3 毫克、6 毫克、12 毫克和 24 毫克）。只有在其他缓解措施失败的情况下，才允许减少剂量以应对胃肠道耐受性。

The ATTAIN Phase 3 global clinical development program for orforglipron has enrolled more than 4,500 people with obesity or overweight across two global registration trials. The program began in 2023 with additional results anticipated this year.

奥格列普隆的ATTAIN3期全球临床开发项目已通过两项全球注册试验招募了4,500多名肥胖或超重患者。该计划于 2023 年开始，预计今年将取得更多成果。