High baseline FGF21 levels are associated with poor glucose-lowering efficacy of exenatide in patients with type 2 diabetes

Abstract

Aims

To investigate the association between fibroblast growth factor 21 (FGF21) levels and glycemic response to exenatide in patients with type 2 diabetes.

Methods

The exploratory analysis of a multi-center trial included 190 patients with type 2 diabetes inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues. All participants received exenatide twice daily as an add-on therapy for 16 weeks. Serum FGF21 and other information at the baseline and end of follow-ups were obtained. Linear regression analysis was used to determine the correlations between baseline FGF21 levels and HbA1c reduction from baseline after the treatment.

Results

After 16 weeks of treatment with exenatide, a decline in the HbA1c levels from baseline was associated with higher baseline FGF21 levels among all participants (r = 0.193, P = 0.008) and in subgroup of the participants receiving background metformin monotherapy (r = 0.231, P = 0.034). Compared with patients in the lowest FGF21 quartile, patients in the highest FGF21 quartile showed a significantly weakened decline in HbA1c levels from baseline among all participants (β = − 0.16 [95% Cl − 0.31 to − 0.01], P < 0.05) and in subgroup of the participants receiving background metformin monotherapy (β = − 0.23 [95% Cl − 0.43 to − 0.03], P < 0.05), after adjusting for the confounding factors, including age, sex, and baseline HbA1c levels.

Conclusions

The high baseline FGF21 levels are associated with poor glycemic responses to exenatide in patients with type 2 diabetes. Therefore, FGF21 could be used as a biomarker for predicting the efficacy of exenatide treatment.

Trial registration

ChiCTR-IPR-15006558, date registered May 27, 2015.

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Fig. 1

Availability of data and materials

The datasets generated during the current study are available from the corresponding authors upon reasonable request.

Abbreviations

FGF21:

Fibroblast growth factor 21

GLP-1RA:

Glucagon-like peptide-1 receptor agonist

HbA1c:

Glycated hemoglobin A1c

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Acknowledgements

We sincerely thank all the investigators from Beijing Hospital; PLA Rocket Forces Characteristic Medical Center; Beijing Tiantan Hospital, Capital Medical University; Beijing Tongren Hospital, Capital Medical University; The First Hospital of Shanxi Medical University; People’s Hospital of Hainan Province; and Peking University Third Hospital. We also thank all the patients whose participation made this study possible.

Funding

This study was supported by research grants from National Key Research and Development Program of China (2018YFC1313900), the National Natural Science Foundation of China (81830022, 81800730, 81670701 and 91749101), and the Capital’s Funds for Health Improvement and Research (2020-3-40914).

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Authors

Contributions

KY performed the experiments, analyzed the data, and drafted the manuscript. HW, RW, WX, QT, and CW performed the experiments. JY helped supervise the project, performed the experiments, and edited the manuscript. TH designed the study, supervised the project, and edited the manuscript. TH is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding authors

Correspondence to Jin Yang or Tianpei Hong.

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The authors declare that there is no duality of interest associated with this manuscript.

Ethical approval

The research protocol was approved by the Medical Ethics Committee of Peking University Third Hospital.

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All participants provided written informed consent before enrollment in this study.

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Yang, K., Wang, H., Wei, R. et al. High baseline FGF21 levels are associated with poor glucose-lowering efficacy of exenatide in patients with type 2 diabetes. Acta Diabetol (2021). https://doi.org/10.1007/s00592-020-01660-z

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Keywords

  • Fibroblast growth factor 21
  • Glucagon-like peptide-1 receptor agonist
  • Therapeutic efficacy
  • Type 2 diabetes