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Effect of pioglitazone on serum FGF23 levels among patients with diabetic kidney disease: a randomized controlled trial

  • Nephrology - Original Paper
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Abstract

Aim

Elevated fibroblast growth factor-23 (FGF23) is an established marker of cardiovascular disease among patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Recently, circulating FGF23 positively correlated with insulin resistance level among patients with CKD. Pioglitazone improves insulin sensitivity and it may have potential for treating CKD-related FGF23 overactivity.

Methods

A randomized, open-label, controlled trial was performed among patients with T2DM and CKD. Eligible participants were randomly assigned to either oral 15 mg/day of pioglitazone (N = 22) or control group (N = 24) for 16 weeks. Serum FGF23 and homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were measured.

Results

Forty-six patients completed the trial. After 16 weeks of treatment, significant decreases in serum intact FGF23 level (median change − 49.01 (IQR, − 103.51 to − 24.53) vs. 1.07 (IQR, − 22.4–39.53) pg/mL, P = 0.01) and HOMA-IR (mean change − 1.41 (95% CI, − 2.24 to − 0.57) vs. − 0.05 (95% CI, − 1.00–0.89), P = 0.031) were observed in the pioglitazone group compared with the control group. HemoglobinA1C also significantly decreased in the pioglitazone group compared with the control group. No difference was found in the changes of serum phosphorus, calcium and serum intact parathyroid hormone between the two groups. Changes of FGF23 were positively associated with changes of HOMA-IR (R = 0.47) and insulin levels (R = 0.47). No serious adverse event was reported during the study.

Conclusion

This study confirmed that pioglitazone effectively reduced serum FGF23 levels and related to improved insulin sensitivity among patients with T2DM and CKD.

Clinical trial registration

TCTR20210316009.

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Availability of data and materials

Data supporting this study are available upon request.

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Acknowledgements

The authors wish to acknowledge the contributions of the following individuals to this study: staff in the Division of Nephrology and Biomedical Clinical Research Center in Phramongkutklao Hospital.

Funding

This study was supported by a grant from the Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, 10400, Thailand

    Wutipong Triwatana, Bancha Satirapoj, Ouppatham Supasyndh & Naowanit Nata

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  1. Wutipong Triwatana
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  2. Bancha Satirapoj
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  3. Ouppatham Supasyndh
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  4. Naowanit Nata
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Correspondence to Bancha Satirapoj.

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The study was approved by the Ethics Committee of the Institute Review Board at the Royal Thai Army Medical Department and was conducted according to the Declaration of Helsinki.

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Triwatana, W., Satirapoj, B., Supasyndh, O. et al. Effect of pioglitazone on serum FGF23 levels among patients with diabetic kidney disease: a randomized controlled trial. Int Urol Nephrol 55, 1255–1262 (2023). https://doi.org/10.1007/s11255-022-03420-0

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