Zhou Yan, Zhu Jiankun, Wu Haiya, Deng Yuying, Ji Qiuhe
Endocrinology Department of Xi'an International Medical Center Hospital, 777 Xitai Road, Gaoxin District, Xi'an, 710100, Shaanxi Province, China.
Lilly Suzhou Pharmaceutical Co. Ltd., 19F, Centre T1, HKRI Taikoo, No. 288, Shimen No.1 Road, Jing'an District, Shanghai, 200041, China.
Diabetes Ther. 2021 Oct;12(10):2677-2690. doi: 10.1007/s13300-021-01139-2. Epub 2021 Aug 28.
In the randomized, open-label, parallel-arm, active-controlled phase III AWARD-CHN2 trial, once-weekly dulaglutide plus concomitant oral antihyperglycemic medications (OAMs) improved HbA1c over 26 weeks compared with once-daily insulin glargine in patients with type 2 diabetes mellitus (T2DM). This post-hoc subgroup analysis of AWARD-CHN2 investigated the pancreatic safety of dulaglutide in Chinese patients with T2DM, stratified by potential influencing factors.
Changes in pancreatic enzyme (pancreatic amylase, total amylase, and lipase) levels over 26 weeks were assessed and stratified by patient age (< 60, ≥ 60 years), sex (female, male), duration of diabetes (< 10, ≥ 10 years), baseline weight (< 70, ≥ 70 kg), BMI (< 25, ≥ 25 kg/m), HbA1c (< 8.5, ≥ 8.5%), triglycerides (< 2.3, ≥ 2.3 mmol/L), and concomitant OAMs (metformin, sulfonylurea, metformin plus sulfonylurea).
A total of 203 Chinese patients with T2DM were included in this post-hoc analysis. Pancreatic enzyme levels increased within the normal range from baseline to Week 26, and no pancreatitis events were confirmed by independent adjudication. Least-squares mean increase in pancreatic amylase (U/L) from baseline to Week 26 was comparable across all subgroups with no statistically (all P-values > 0.05) or clinically significant between-group differences for age (< 60 years: 5.34; ≥ 60 years: 6.71), sex (female: 5.85; male: 5.66), duration of diabetes (< 10 years: 6.15; ≥ 10 years: 4.85), weight (< 70 kg: 6.19; ≥ 70 kg: 5.39), BMI (< 25 kg/m: 5.92; ≥ 25 kg/m: 5.61), HbA1c (< 8.5%: 6.82; ≥ 8.5%: 4.08), triglycerides (< 2.3 mmol/L: 4.94; ≥ 2.3 mmol/L: 8.04), and concomitant OAMs (metformin: 5.68; sulfonylurea: 5.44; metformin plus sulfonylurea: 5.87). Similar results were observed for total amylase and lipase.
In Chinese patients with T2DM receiving dulaglutide 1.5 mg in AWARD-CHN2, elevations of pancreatic enzymes over 26 weeks were within the normal range and were neither associated with pancreatitis nor baseline factors, which suggests the clinical use of dulaglutide in Chinese patients with T2DM is not associated with pancreatic safety issues.
NCT01648582.
在随机、开放标签、平行组、活性药物对照的III期AWARD-CHN2试验中，与每日一次的甘精胰岛素相比，每周一次的度拉糖肽联合口服降糖药物（OAM）在26周内改善了2型糖尿病（T2DM）患者的糖化血红蛋白（HbA1c）水平。这项AWARD-CHN2的事后亚组分析按潜在影响因素分层，研究了度拉糖肽在中国T2DM患者中的胰腺安全性。
评估26周内胰腺酶（胰淀粉酶、总淀粉酶和脂肪酶）水平的变化，并按患者年龄（<60岁、≥60岁）、性别（女性、男性）、糖尿病病程（<10年、≥10年）、基线体重（<70kg、≥70kg）、体重指数（BMI，<25kg/m²、≥25kg/m²）、HbA1c（<8.5%、≥8.5%）、甘油三酯（<2.3mmol/L、≥2.3mmol/L）以及联合使用的OAM（二甲双胍、磺脲类药物、二甲双胍加磺脲类药物）进行分层。
这项事后分析共纳入203例中国T2DM患者。胰腺酶水平从基线到第26周在正常范围内升高，且独立判定未确认胰腺炎事件。从基线到第26周，所有亚组中胰淀粉酶（U/L）的最小二乘均值升高具有可比性，年龄（<60岁：5.34；≥60岁：6.71）、性别（女性：5.85；男性：5.66）、糖尿病病程（<10年：6.15；≥10年：4.85）、体重（<70kg：6.19；≥70kg：5.39）、BMI（<25kg/m²：5.92；≥25kg/m²：5.61）、HbA1c（<8.5%：6.82；≥8.5%：4.08）、甘油三酯（<2.3mmol/L：4.94；≥2.3mmol/L：8.04）以及联合使用的OAM（二甲双胍：5.68；磺脲类药物：5.44；二甲双胍加磺脲类药物：5.87）之间无统计学（所有P值>0.05）或临床显著的组间差异。总淀粉酶和脂肪酶也观察到类似结果。
在AWARD-CHN2试验中接受1.5mg度拉糖肽治疗的中国T2DM患者中，26周内胰腺酶升高在正常范围内，与胰腺炎或基线因素均无关，这表明度拉糖肽在中国T2DM患者中的临床应用与胰腺安全性问题无关。
NCT01648582。
