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The Effect of BMI on Pharmacokinetic and Pharmacodynamic Parameters of Insulin Degludec: Results from an Euglycemic Glucose Clamp Study

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Abstract

Purpose

This study evaluated the effect of body mass index (BMI) on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of insulin degludec in healthy Chinese males, depending on an euglycemic glucose clamp study.

Methods

Sixty-five healthy male subjects were divided into four groups according to quartile of BMI value. Group A: BMI ≤ 20.7 kg/m2; group B: 20.7 < BMI ≤ 22.5 kg/m2; group C: 22.5 < BMI ≤ 23.6 kg/m2; group D: BMI > 23.6 kg/m2. Each volunteer received a single subcutaneous dose (0.4 U/kg) of insulin degludec and accepted a 24-h euglycemic glucose clamp study. The primary PK parameters were maximum observed drug concentration (Cmax) and the area under the curve (AUCINS) for the specified time intervals. The primary PD parameters were the time to the start of glucose infusion (Tonset), maximal glucose infusion rate (GIRmax) and area under the curve (AUCGIR) for the specified time intervals. The differences of these PK/PD parameters were compared among groups.

Results

Cmax and the AUC of insulin (0–6 h, 6–12 h and 0–24 h) were more than onefold higher in group A than those in groups B, C, D, and the concentration-time curve of group A was significantly shifted to the left compared with the other three groups. The GIRmax, total AUCGIR, and AUCGIR for each time interval were significantly higher in group A than those in other three groups. The proportion of AUCGIR in group A was the lowest proportion among four groups seen in the late stage. Multiple linear regression analysis showed that BMI was negatively correlated with AUCGIR,0-24 h.

Conclusions

Insulin degludec in healthy Chinese male subjects with BMI ≤ 20.7 kg/m2 had a faster absorption, clearance, and a stronger glucose-lowering effect, but a steeper decrease of insulin action in the late stage after dosing.

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Authors and Affiliations

  1. Health Management Center, General Practice Center, West China Hospital, Sichuan University, Chengdu, China

    Ting Li

  2. Department of General Practice, West China Hospital, Sichuan University, Chengdu, China

    Hui Liu

  3. Department of Neurology, Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Sichuan Bayi Rehabilitation Center, Chengdu, China

    Songlin Li

  4. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China

    Hongling Yu, Jiaqi Li, Huiwen Tan & Yerong Yu

Authors
  1. Ting Li
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Corresponding author

Correspondence to Yerong Yu.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Ting Li, Hui Liu, Songlin Li, Hongling Yu, Jiaqi Li, Huiwen Tan, and Yerong Yu declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Author contributions

All the authors contributed to the study design, conduct, and/or data collection. TL and HL: study design, conduct, data collection, data analysis and writing manuscript. SL, HY, JL and HT: study design, conduct, data collection. YY: study design, supervision and revising manuscript.

Ethics approval

This study was performed in accordance with Good Clinical Practice and conformed to the ethical principles of the Declaration of Helsinki. Meanwhile the study was approved by an independent ethics committee of the West China Hospital of Sichuan University. All subjects wrote informed consent after a detailed explanation of the study protocol.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Not applicable.

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Not applicable.

Supplementary Information

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Supplementary file1 (DOCX 508 KB)

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Li, T., Liu, H., Li, S. et al. The Effect of BMI on Pharmacokinetic and Pharmacodynamic Parameters of Insulin Degludec: Results from an Euglycemic Glucose Clamp Study. Clin Pharmacokinet 62, 449–456 (2023). https://doi.org/10.1007/s40262-022-01207-1

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  • DOI: https://doi.org/10.1007/s40262-022-01207-1

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