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Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

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Abstract

This meta-analysis aims to evaluate the impact of Sodium Glucose Transporter 2 (SGLT2) inhibitors on fractures, bone mineral density (BMD), and bone metabolism markers in type 2 diabetes mellitus (T2DM) patients. Pooled relative risk (RR) with 95% confidence interval (CI) assessed the relationship between SGLT2 inhibitors and fracture risk. Weighted mean difference (WMD) with 95% CI explored the correlation between SGLT2 inhibitors and BMD, as well as bone metabolism markers. A total of 20 randomised controlled trials (RCTs) involving 12,764 patients were analysed. No significant association emerged between SGLT2 inhibitor use and elevated fracture risk (pooled RR = 1.21, 95% CI [0.95, 1.54], I2 = 22%). Furthermore, SGLT2 inhibitors exhibited no substantial effects on BMD changes at the lumbar spine (WMD = -0.02, 95% CI [-0.38, 0.34]), femoral neck (WMD = 0.11, 95% CI [-0.28, 0.50]), total hip (WMD = -0.20, 95% CI [-0.41, 0.01]), and distal forearm (WMD = -0.20, 95% CI [-0.62, 0.22]). Similarly, no notable impact of SGLT2 inhibitors on bone metabolism markers, including CTX (WMD = 0.04, 95% CI [-0.02, 0.09]), P1NP (WMD = 1.06, 95% CI [-0.44, 2.57]), PTH (WMD = 0.34, 95% CI [-0.07, 0.75]), calcium (WMD = 0.01, 95% CI [-0.02, 0.04]), and phosphate (WMD = 2.37, 95% CI [-0.76, 5.49]). The findings suggest that the utilization of SGLT2 inhibitors is not significantly linked to an elevated risk of fractures in individuals with T2DM. However, further clinical investigations and extended follow-up periods are warranted to establish more conclusive determinations.

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Data Availability

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

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Acknowledgements

The research design was carried out by WWB and LYJ. Literature retrieval and screening, data extraction, data analysis, statistical analysis, and written contributions were performed by WX, ZFY, ZYF, and ZJY. The manuscript was revised by WWB and SYL. All authors reviewed the manuscript, and all authors have read and approved the final version of the manuscript.

Funding

This research was funded by the Natural Science Foundation of Shandong Province (ZR2020MH361), the Shandong Provincial Traditional Chinese Medicine Science and Technology Project (2020M023), the Shandong Provincial Medical and Health Science and Technology Development Program Project (2019WS562), China Postdoctoral Science Foundation (2021M692750), and Special funding for Mount Tai Scholar Project.

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Authors and Affiliations

  1. Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China

    Xin Wang, Fengyi Zhang, Yufeng Zhang & Jiayi Zhang

  2. Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, 250014, People’s Republic of China

    Yingli Sheng

  3. Shandong University of Traditional Chinese Medicine Second Affiliated Hospital, Jinan, 250001, People’s Republic of China

    Wenbo Wang & Yujie Li

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  1. Xin Wang
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Correspondence to Wenbo Wang.

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Wang, X., Zhang, F., Zhang, Y. et al. Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Osteoporos Int 34, 2013–2025 (2023). https://doi.org/10.1007/s00198-023-06908-2

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