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Pharmacokinetics, Pharmacodynamics and Safety of Janagliflozin in Chinese Type 2 Diabetes Mellitus Patients with Renal Impairment

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Abstract

Background

Janagliflozin is a novel sodium–glucose cotransport-2 inhibitor. Despite its remarkable effect in glycemic control, no systematic research has evaluated the effect of renal impairment (RI) on its pharmacokinetics and pharmacodynamics.

Methods

Here, patients with T2DM (n = 30) were divided into normal renal function (eGFR ≥ 90 mL/min/1.73 m2), mild RI (eGFR between 60 and 89 mL/min/1.73 m2), moderate RI-I (eGFR between 45 and 59 mL/min/1.73 m2), and moderate RI-II (eGFR between 30 and 44 mL/min/1.73 m2) groups. They were administered 50 mg janagliflozin orally, and plasma and urine samples were collected for the determination of janagliflozin concentration.

Results

Following oral administration, janagliflozin was rapidly absorbed, with the time to Cmax of 2–6 h for janagliflozin and 3–6 h for its metabolite XZP-5185. Plasma exposure levels were similar for janagliflozin in T2DM patients with or without RI but decreased for the metabolite XZP-5185 in T2DM patients with eGFR between 45 and 89 mL/min/1.73 m2. Janagliflozin significantly promoted the excretion of urinary glucose, even in patients with reduced eGFR. Janagliflozin was well tolerated in patients with T2DM with or without RI, and no serious adverse events (SAEs) occurred during this trial.

Conclusions

The exposure levels of janagliflozin in T2DM patients were slightly increased with worsening of RI (i.e., 11% increase in the AUC in patients with moderate RI compared with the normal renal function group). Despite worsening of renal function, janagliflozin exerted a significant pharmacologic effect and was well tolerated, even in patients with moderate RI, implying a promising role in the treatment of patients with in T2DM.

Registration

China Drug Trial register (http://www.chinadrugtrials.org.cn/I) identifier no.: CTR20192721.

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Acknowledgements

The authors thank the volunteers for their participation and cooperation. We greatly appreciate Shandong Xuanzhu Pharma Co. Ltd. and Beijing Sihuan Pharma Co. Ltd. for their kind support. We would like to thank Editage (www.editage.cn) for English language editing.

Author information

Author notes

  1. Hengli Zhao and Zhirui Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Research Center, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Li Xia District, Jinan, 250013, People’s Republic of China

    Hengli Zhao, Kun He, Wenyu Zhang & Qing Wen

  2. Department of Renal Division, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing, 100029, People’s Republic of China

    Zhirui Zhao & Hong Cheng

  3. Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Li Xia District, Jinan, 250013, People’s Republic of China

    Nianrong Mi, Kai Lou, Xiaolin Dong & Shuguang Pang

  4. Jilin Huisheng Biopharmaceutical Co., Ltd., Jilin, 135000, People’s Republic of China

    Jingfang Sun & Xinyu Hu

Authors
  1. Hengli Zhao
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Corresponding authors

Correspondence to Shuguang Pang, Hong Cheng or Qing Wen.

Ethics declarations

Funding

This work was supported by the National Science and Technology Major Project of China (2020ZX09201-025), the Natural Science Foundation of China (81901610) and the Jinan Technology Development Program (202019118).

Trial registration

The trial registration number is CTR20192721, registered on 12 February 2020.

Conflict of interest

Hengli Zhao, Zhirui Zhao, Kun He, Nianrong Mi, Kai Lou, Xiaolin Dong, Wenyu Zhang, Jingfang Sun, Xinyu Hu, Shuguang Pang, Hong Cheng, and Qing Wen declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval

The conduct of the clinical trial was approved by the independent ethics committee of Jinan Central Hospital (Jinan, China) and Beijing Anzhen Hospital (Beijing, China). The trial was performed according to the ethical principles of the Declaration of Helsinki (revised in 2013) and those of the International Conference on Harmonization guideline E6: Good Clinical Practice.

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Not applicable.

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Not applicable.

Availability of data and material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

Author contributions

All authors contributed to the studies and manuscript. QW, HC, and SGP designed and supervised the study; HLZ, ZRZ, KH, NRM, KL, and XLD performed and executed the study; HLZ, WYZ, JFS, and XYH analyzed and interpreted the data; HLZ wrote the initial draft; all authors critically reviewed or revised the draft of the manuscript and approved the final manuscript.

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Zhao, H., Zhao, Z., He, K. et al. Pharmacokinetics, Pharmacodynamics and Safety of Janagliflozin in Chinese Type 2 Diabetes Mellitus Patients with Renal Impairment. Clin Pharmacokinet 62, 1093–1103 (2023). https://doi.org/10.1007/s40262-023-01256-0

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  • DOI: https://doi.org/10.1007/s40262-023-01256-0

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