Efficacy and safety of cofrogliptin once every 2 weeks in Chinese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, phase 3 trial

Leili Gao; Fang Bian; Tianrong Pan; Hongwei Jiang; Bo Feng; Chengxia Jiang; Jia Sun; Jianzhong Xiao; Pangke Yan; Linong Ji

doi:10.1111/dom.16014

Efficacy and safety of cofrogliptin once every 2 weeks in Chinese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, phase 3 trial

Diabetes Obes Metab. 2024 Oct 21. doi: 10.1111/dom.16014. Online ahead of print.

Authors

Leili Gao¹, Fang Bian², Tianrong Pan³, Hongwei Jiang⁴, Bo Feng⁵, Chengxia Jiang⁶, Jia Sun⁷, Jianzhong Xiao⁸, Pangke Yan⁹, Linong Ji¹

Affiliations

¹ Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
² Department of Endocrinology, Cangzhou People's Hospital, Cangzhou, China.
³ Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University Hefei, Hefei, China.
⁴ Department of Endocrinology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
⁵ Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Department of Endocrinology, The Second People's Hospital of Yibin, Yibin, China.
⁷ Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
⁸ Department of Endocrinology, Beijing Tsinghua Changgung Hospital, Beijing, China.
⁹ Haisco Pharmaceutical Group Co. Ltd., Chengdu, China.

PMID: 39434431
DOI: 10.1111/dom.16014

Abstract

Aim: 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).

Materials and methods: 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_1c) from baseline to week 24.

Results: 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_1c 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_1c 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.

Conclusions: Cofrogliptin provided glycaemic control over 52 weeks and was generally well tolerated in patients with T2D.

Clinical trial registration: Registered on Clinicaltrials.gov with the registration number NCT04556851 (https://clinicaltrials.gov/study/NCT04556851).

Keywords: cofrogliptin; glycated haemoglobin; long‐acting DPP4‐inhibitor; randomized controlled trial; type 2 diabetes.

Associated data

ClinicalTrials.gov/NCT04556851

Grants and funding

Haisco Pharmaceutical Group Co. Ltd