2026年2月26日，ACHIEVE-3研究结果发表于《柳叶刀》。作为该系列首个头对头研究，ACHIEVE-3研究评估了orforglipron对比口服司美格鲁肽，用于二甲双胍控制不佳的2型糖尿病患者的疗效与安全性。

orforglipron是一种小分子口服胰高糖素样肽1（GLP-1）受体激动剂，服药不受饮食或饮水限制。该研究为期52周，共纳入1,698名受试者，随机分配至四个活性治疗组：orforglipron 12mg、36mg，或口服司美格鲁肽7mg、14mg。

结果显示，orforglipron在主要终点及所有关键次要终点均优于对照组，糖化血红蛋白（HbA_1c）降幅与体重改善均显著提升。

据悉，礼来公司已向全球40多个国家监管机构提交orforglipron上市申请，美国FDA预计2026年第二季度就肥胖适应症作出审批决定。

Orforglipron是一种在研的每日一次口服小分子（非肽类）GLP-1受体激动剂，全天任意时间服用，不受饮食饮水限制。该分子由中外制药发现，2018年授权礼来开发，双方共同发表临床前药理学数据。目前礼来正推进其3期临床开发，覆盖2型糖尿病、肥胖或伴体重相关合并症的超重成人体重管理，并探索其在肥胖成人阻塞性睡眠呼吸暂停及高血压治疗中的潜在应用。

信源

[1]All measures except for body weight for orforglipron 12 mg vs. oral semaglutide 14 mg and percentage of participants achieving A1C <5.7% were controlled for family-wise type 1 error using the efficacy estimand and treatment-regimen estimand. Body weight for orforglipron 12 mg vs. oral semaglutide 14 mg and percentage of participants achieving A1C <5.7% were prespecified secondary endpoints and showed nominal statistical significance using the efficacy estimand.

[2]The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and/or dose modifications) for 52 weeks without initiating additional antihyperglycemic medications (>14 days of use). 

[3]The treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of additional antihyperglycemic medications.

[4]Ma X, Liu R, Pratt EJ, Benson CT, Bhattachar SN, Sloop KW. Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist. Diabetes Ther. 2024 Apr;15(4):819-832. https://doi.org/10.1007/s13300-024-01554-1. Epub 2024 Feb 24. PMID: 38402332; PMCID: PMC10951152.

[5]Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, & Sloop KW, Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist, Proc. Natl. Acad. Sci. U.S.A. 117 (47) 29959-29967, https://doi.org/10.1073/pnas.2014879117 (2020).