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Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials

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Abstract

Summary

Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433).

Introduction

Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients.

Methods

Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials.

Results

There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03–0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ‰), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons.

Conclusion

The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture.

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Funding

The present study was supported by grants from the National Natural Science Foundation of China (grant no. 81774344).

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Author notes

  1. Y. S. Zhang, W. Y. Weng and B. C. Xie contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China

    Y. S. Zhang, W. Y. Weng, B. C. Xie, Y. Meng, Y. H. Hao, Y. M. Liang & Z. K. Zhou

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  1. Y. S. Zhang
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  2. W. Y. Weng
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  3. B. C. Xie
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  4. Y. Meng
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  7. Z. K. Zhou
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Correspondence to Z. K. Zhou.

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Zhang, Y.S., Weng, W.Y., Xie, B.C. et al. Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials. Osteoporos Int 29, 2639–2644 (2018). https://doi.org/10.1007/s00198-018-4649-8

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  • DOI: https://doi.org/10.1007/s00198-018-4649-8

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