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Background <p>DPP-4 inhibitors are a class of oral hypoglycemic drugs commonly used in the treatment of type 2 diabetes mellitus (T2DM). Fultagliptin benzoate is a novel and high-selective DPP-4 inhibitor. The renal excretion of many medications, including DPP-4 inhibitors, can be altered in patients with renal impairment. This study investigates the pharmacokinetics, pharmacodynamics, and safety of fultagliptin benzoate tablets in mild and moderate renal impairment (RI) compared with normal renal function to ensure safety and efficacy across these groups.</p> Methods <p>A single-dose, non-randomized, open-label, and parallel-control phase I study was performed. Pharmacokinetics, pharmacodynamics, and safety of fultagliptin benzoate tablets were evaluated.</p> Results <p>A total of 18 participants were enrolled and completed the study. After oral administration of a single dose of fultagliptin benzoate tablets 12&#xa0;mg under fasted conditions, fultagliptin was absorbed with median time to reach peak concentration (<i>T</i><sub>max</sub>) of 4.50, 3.00, and 5.50&#xa0;hours in healthy participants, patients with mild RI, and patients with moderate RI, respectively, and eliminated with mean elimination half-life (<i>t</i><sub>½</sub>) of 32.27, 40.22, and 46.38&#xa0;h, respectively. Compared with healthy participants, patients with mild RI had similar peak concentration (<i>C</i><sub>max</sub>), while area under the concentration–time curve from time zero to the last measured concentration (AUC<sub>0–<i>t</i></sub>) and AUC from time zero to infinity (AUC<sub>0–∞</sub>) increased by 24.7% and 25.0%, respectively. In patients with moderate RI, <i>C</i><sub>max</sub>, AUC<sub>0–<i>t</i></sub>, and AUC<sub>0–∞</sub> increased by 27.5%, 86.4%, and 87.9%, respectively. Comparing the renal clearance rate (CL<sub>R</sub>) with that of the healthy participants (8.96&#xa0;± 2.24&#xa0;L/h), the CL<sub>R</sub> values (mean ± SD) of patients with mild RI and patients with moderate RI were 6.615&#xa0;± 1.34&#xa0;L/h and 4.54&#xa0;± 1.20&#xa0;L/h, respectively, which were approximately 73.8% and 50.6% of that of the healthy participants. For pharmacodynamic biomarkers, the DPP-4 inhibition rate (<i>E</i><sub>max</sub>) in all groups of participants was &gt;&#xa0;90%. The duration of DPP-4 inhibition rate over 80% in the three groups showed an increasing trend. Fultagliptin benzoate tablets were well tolerated in all participants during the study.</p> Conclusion <p>In patients with mild RI, the small increase in exposure to fultagliptin was not considered clinically relevant. Although a significant increase in exposure was observed in patients with moderate RI without eliciting issues related to efficacy and safety, a half-dose reduction may be considered for the protection of participants.</p> Trial Registration <p>ClinicalTrials.gov (NCT06883656); registered 12 March 2025 (retrospectively registered).</p>

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Pharmacokinetics, Pharmacodynamics and Safety of Fultagliptin Benzoate Tablets, a DPP-4 Inhibitor, in Patients With Varying Degrees of Renal Insufficiency and Matched Healthy Volunteers: A Phase I Clinical Trial

  • 期刊论文

  • 发表日期：

    2026年2月9日

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  • Yue Chen,
  • Chao Hu,
  • Xiaotao Cao,
  • Yuchun Men,
  • Ying Wang,
  • Ruijie Zhang,
  • Hongyu Guan,
  • Lihong Shi,
  • Fang Liu,
  • Jia Miao

摘要

Background

DPP-4 inhibitors are a class of oral hypoglycemic drugs commonly used in the treatment of type 2 diabetes mellitus (T2DM). Fultagliptin benzoate is a novel and high-selective DPP-4 inhibitor. The renal excretion of many medications, including DPP-4 inhibitors, can be altered in patients with renal impairment. This study investigates the pharmacokinetics, pharmacodynamics, and safety of fultagliptin benzoate tablets in mild and moderate renal impairment (RI) compared with normal renal function to ensure safety and efficacy across these groups.

Methods

A single-dose, non-randomized, open-label, and parallel-control phase I study was performed. Pharmacokinetics, pharmacodynamics, and safety of fultagliptin benzoate tablets were evaluated.

Results

A total of 18 participants were enrolled and completed the study. After oral administration of a single dose of fultagliptin benzoate tablets 12 mg under fasted conditions, fultagliptin was absorbed with median time to reach peak concentration (Tmax) of 4.50, 3.00, and 5.50 hours in healthy participants, patients with mild RI, and patients with moderate RI, respectively, and eliminated with mean elimination half-life (t½) of 32.27, 40.22, and 46.38 h, respectively. Compared with healthy participants, patients with mild RI had similar peak concentration (Cmax), while area under the concentration–time curve from time zero to the last measured concentration (AUC0–t) and AUC from time zero to infinity (AUC0–∞) increased by 24.7% and 25.0%, respectively. In patients with moderate RI, Cmax, AUC0–t, and AUC0–∞ increased by 27.5%, 86.4%, and 87.9%, respectively. Comparing the renal clearance rate (CLR) with that of the healthy participants (8.96 ± 2.24 L/h), the CLR values (mean ± SD) of patients with mild RI and patients with moderate RI were 6.615 ± 1.34 L/h and 4.54 ± 1.20 L/h, respectively, which were approximately 73.8% and 50.6% of that of the healthy participants. For pharmacodynamic biomarkers, the DPP-4 inhibition rate (Emax) in all groups of participants was > 90%. The duration of DPP-4 inhibition rate over 80% in the three groups showed an increasing trend. Fultagliptin benzoate tablets were well tolerated in all participants during the study.

Conclusion

In patients with mild RI, the small increase in exposure to fultagliptin was not considered clinically relevant. Although a significant increase in exposure was observed in patients with moderate RI without eliciting issues related to efficacy and safety, a half-dose reduction may be considered for the protection of participants.

Trial Registration

ClinicalTrials.gov (NCT06883656); registered 12 March 2025 (retrospectively registered).