Gao Leili, Bian Fang, Pan Tianrong, Jiang Hongwei, Feng Bo, Jiang Chengxia, Sun Jia, Xiao Jianzhong, Yan Pangke, Ji Linong
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
Department of Endocrinology, Cangzhou People's Hospital, Cangzhou, China.
Diabetes Obes Metab. 2025 Jan;27(1):280-290. doi: 10.1111/dom.16014. Epub 2024 Oct 21.
We conducted a multicentre, randomized phase 3 trial in China to evaluate the efficacy and safety of cofrogliptin (HSK7653), a novel long-acting dipeptidyl peptidase-4 inhibitor, in patients with drug-naïve type 2 diabetes (T2D).
Patients with inadequately controlled T2D were randomly assigned (1:1:1) to cofrogliptin 10 mg, cofrogliptin 25 mg or placebo, taken orally once every 2 weeks for a 24-week double-blind period. Eligible patients then received cofrogliptin 25 mg in a 28-week open-label extension. The primary endpoint was the change in glycated haemoglobin (HbA) from baseline to week 24.
In total, 475 patients (median age: 54.0 years) were randomized and received at least one dose of cofrogliptin 10 mg (n = 158), cofrogliptin 25 mg (n = 158) or placebo (n = 159); 401 patients entered the open-label extension. At week 24, the least-squares (LS) mean difference (95% confidence interval [CI]) in HbA versus placebo was -0.63% (-0.81, -0.46) with cofrogliptin 10 mg and -0.59% (-0.77, -0.42) with cofrogliptin 25 mg (both p < 0.0001). The LS mean (standard error) change in HbA from baseline was maintained at the end of the study in patients given open-label cofrogliptin 25 mg for an additional 28 weeks: cofrogliptin 10 mg: -0.86% (0.07); cofrogliptin 25 mg: -0.74% (0.07); placebo: -0.89% (0.07). Over the entire study, common adverse events were hyperuricaemia, hyperlipidaemia, hypertriglyceridaemia, increased lipase, upper respiratory tract infection and urinary tract infection. Hypoglycaemic events did not significantly differ between groups.
Cofrogliptin provided glycaemic control over 52 weeks and was generally well tolerated in patients with T2D.
Registered on Clinicaltrials.gov with the registration number NCT04556851 (https://clinicaltrials.gov/study/NCT04556851).
我们在中国开展了一项多中心、随机3期试验，以评估新型长效二肽基肽酶-4抑制剂科罗格列净（HSK7653）在初治2型糖尿病（T2D）患者中的疗效和安全性。
T2D控制不佳的患者被随机分配（1:1:1）至科罗格列净10毫克、科罗格列净25毫克或安慰剂组，每2周口服一次，为期24周的双盲期。符合条件的患者随后进入为期28周的开放标签延长期，接受科罗格列净25毫克治疗。主要终点是糖化血红蛋白（HbA）从基线至第24周的变化。
总共475例患者（中位年龄：54.0岁）被随机分组并接受至少一剂科罗格列净10毫克（n = 158）、科罗格列净25毫克（n = 158）或安慰剂（n = 159）；401例患者进入开放标签延长期。在第24周时，科罗格列净10毫克组与安慰剂相比，HbA的最小二乘（LS）均值差异（95%置信区间[CI]）为-0.63%（-0.81，-0.46），科罗格列净25毫克组为-0.59%（-0.77，-0.42）（均p < 0.0001）。在研究结束时，接受开放标签科罗格列净25毫克治疗额外28周的患者中，HbA从基线的LS均值（标准误）变化得以维持：科罗格列净10毫克组：-0.86%（0.07）；科罗格列净25毫克组：-0.74%（0.07）；安慰剂组：-0.89%（0.07）。在整个研究中，常见不良事件为高尿酸血症、高脂血症、高甘油三酯血症、脂肪酶升高、上呼吸道感染和尿路感染。低血糖事件在各组之间无显著差异。
科罗格列净在52周内实现了血糖控制，且T2D患者总体耐受性良好。
在Clinicaltrials.gov上注册，注册号为NCT04556851（https://clinicaltrials.gov/study/NCT04556851）。
