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Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis

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Abstract

Summary

Previous evidence suggests that bisphosphonates may improve glycemic control. The present meta-analysis, comprising seven studies with 1,233,844 participants, demonstrated that bisphosphonate use was significantly associated with a lower risk of diabetes. However, in the randomized controlled trial subgroup, a non-significant association was found. Further studies are needed to determine causality.

Purpose

This study aimed to evaluate the impact of bisphosphonates on glycemic control and the risk of incident diabetes.

Methods

MEDLINE, Embase, and Cochrane Library were searched from inception to February 15, 2022. Experimental or observational studies that compared fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels and the diabetes risk with and without bisphosphonates were included. Studies without relevant outcomes, only providing crude estimates, or the absence of a control group were excluded. Two reviewers independently screened the articles, extracted data, and appraised studies. The pooled relative risk (RR) and weighted mean difference (WMD) were calculated using random effects models.

Results

Seven studies (n = 1,233,844) on diabetes risk were included, including two post hoc analyses of randomized controlled trials (RCTs) and five observational studies. Compared with controls, bisphosphonates (BPs) were associated with a significant decrease in the risk of diabetes (RR = 0.77; 95% CI, 0.65 to 0.90; P = 0.002). However, in the subgroup of post hoc analyses of RCTs, the association was non-significant (RR = 0.93; 95% CI, 0.74 to 1.18; P = 0.576). Moreover, three studies (n = 4906) on FBG and one (n = 60) on HbA1c were included. We observed non-significant association between BPs and changes in FBG (WMD =  − 0.61 mg/dL; 95% CI, − 2.72 to 1.49; P = 0.567) and HbA1c (WMD =  − 0.11%; 95% CI, − 0.23 to 0.01; P = 0.083).

Conclusion

Patients taking BPs may have a lower risk of incident diabetes than those without BPs. However, due to the high between-study heterogeneity and inconsistent findings between post hoc analyses of RCTs and observational studies, further rigorous RCTs are required to determine whether the findings are causal.

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Data Availability

The datasets analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Rd., 97002, Hualien, Taiwan

    Po-Wei Chen & Shu-Man Lin

  2. Medical Department, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Rd., 97002, Hualien, Taiwan

    Po-Wei Chen

  3. Department of Psychiatric, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Rd., Hualien, 97002, Taiwan

    Hsiao-Yuan Su

  4. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    Yu-Kang Tu & Huei-Kai Huang

  5. Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, Taipei, Taiwan

    Yu-Kang Tu

  6. Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chih-Hsing Wu

  7. Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chih-Hsing Wu

  8. Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chih-Hsing Wu

  9. School of Medicine, Tzu Chi University, Hualien, Taiwan

    Jih-I Yeh, Ching-Hui Loh, Huei-Kai Huang & Shu-Man Lin

  10. Department of Family Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Rd., Hualien, 97002, Taiwan

    Jih-I Yeh & Huei-Kai Huang

  11. Library, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Rd., Hualien, 97002, Taiwan

    Li-Yu Chen

  12. Section of Endocrinology, Diabetes, Nutrition & Weight Management, Boston University School of Medicine, MA, Boston, USA

    Carol Chiung-Hui Peng

  13. Center for Aging and Health, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Rd., Hualien, 97002, Taiwan

    Ching-Hui Loh

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Chen, PW., Su, HY., Tu, YK. et al. Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis. Osteoporos Int 34, 387–397 (2023). https://doi.org/10.1007/s00198-022-06616-3

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