Onishi Yukiko, Oura Tomonori, Takeuchi Masakazu
Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Tokyo, Japan.
Japan Drug Development and Medical Affairs, Eli Lilly Japan K.K, Kobe, 651-0086, Japan.
Diabetes Ther. 2024 Mar;15(3):649-661. doi: 10.1007/s13300-024-01534-5. Epub 2024 Feb 4.
The presence of metabolic abnormalities in patients with type 2 diabetes (T2D) increases the risk of cardiovascular disease and other comorbidities. This analysis compared the effects of tirzepatide (5, 10, and 15 mg) and dulaglutide 0.75 mg on the prevalence of metabolic abnormalities in Japanese patients with T2D.
This was a post hoc analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled, parallel-group, phase 3 trial that compared the efficacy and safety of tirzepatide monotherapy (5, 10, and 15 mg) to dulaglutide 0.75 mg in Japanese patients with T2D. Thresholds for abnormalities were based on the Japanese criteria for metabolic syndrome. Proportions of participants meeting a composite endpoint (visceral fat accumulation measured by waist circumference plus two or more of dyslipidemia, hypertension, or hyperglycemia) or individual component thresholds were calculated at baseline and week 52 for the overall population and for baseline body mass index (BMI) subgroups (< 25, 25 to < 30, and ≥ 30 kg/m).
Of 636 randomized participants, 431 (67.8%) met the composite endpoint at baseline, with similar findings observed across treatment arms. At week 52, the proportion of participants on treatment that met the composite endpoint was 31.7%, 23.0%, and 14.2% in the tirzepatide 5-, 10-, and 15-mg arms, respectively, and 56.5% in the dulaglutide arm (p < 0.001). A higher proportion met the composite endpoint at baseline in the BMI 25 to < 30 and ≥ 30 kg/m subgroups (73.2-79.3%) compared with the < 25 kg/m subgroup (45.3%), with reductions observed across all BMI subgroups treated with tirzepatide. The proportion of participants with individual metabolic abnormalities showed similar trends to those observed for the composite endpoint. Tirzepatide was consistently superior to dulaglutide across all assessments.
Tirzepatide reduced the prevalence of multiple metabolic abnormalities, indicating tirzepatide may have metabolic benefit in Japanese patients with T2D.
ClinicalTrials.gov, NCT03861052.
2型糖尿病（T2D）患者存在代谢异常会增加心血管疾病和其他合并症的风险。本分析比较了替尔泊肽（5、10和15毫克）与度拉糖肽0.75毫克对日本T2D患者代谢异常患病率的影响。
这是对SURPASS J-mono试验的事后分析，该试验是一项多中心、随机、双盲、活性对照、平行组3期试验，比较了替尔泊肽单药治疗（5、10和15毫克）与度拉糖肽0.75毫克在日本T2D患者中的疗效和安全性。异常阈值基于日本代谢综合征标准。在基线和第52周计算总体人群以及基线体重指数（BMI）亚组（<25、25至<30和≥30kg/m²）中达到复合终点（通过腰围测量的内脏脂肪堆积加上血脂异常、高血压或高血糖中的两项或更多项）或个体成分阈值的参与者比例。
在636名随机参与者中，431名（67.8%）在基线时达到复合终点，各治疗组的结果相似。在第52周时，替尔泊肽5毫克、10毫克和15毫克组中达到复合终点的治疗参与者比例分别为31.7%、23.0%和14.2%，度拉糖肽组为56.5%（p<0.001）。与BMI<25kg/m²亚组（45.3%）相比，BMI在25至<30kg/m²和≥30kg/m²亚组中在基线时达到复合终点的比例更高（73.2 - 79.3%），在接受替尔泊肽治疗的所有BMI亚组中均观察到比例降低。具有个体代谢异常的参与者比例显示出与复合终点相似的趋势。在所有评估中，替尔泊肽始终优于度拉糖肽。
替尔泊肽降低了多种代谢异常的患病率，表明替尔泊肽可能对日本T2D患者有代谢益处。
ClinicalTrials.gov，NCT03861052。
