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Glucose-Lowering Drugs and Fracture Risk—a Systematic Review

  • Bone and Diabetes (A Schwartz and P Vestergaard, Section Editors)
  • Published:
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Abstract

Purpose of Review

Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses.

Recent Findings

Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium–glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men.

Summary

New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.

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Funding

This work has received funding by Steno Collaborative grant, Novo Nordisk Foundation Denmark (Grant no. NNF18OC0052064).

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Authors and Affiliations

  1. Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

    Z. Al-Mashhadi, R. Fuglsang-Nielsen, S. Gregersen & Jakob Starup-Linde

  2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Z. Al-Mashhadi & B. Langdahl

  3. Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark

    R. Viggers

  4. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    R. Viggers

  5. Department of Internal Medicine, Regional Hospital Horsens, Horsens, Denmark

    R. Fuglsang-Nielsen

  6. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands

    F. de Vries

  7. Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands

    F. de Vries

  8. Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands

    J. P. van den Bergh

  9. Department of Internal Medicine, VieCuri Medical Centre, Venlo, The Netherlands

    J. P. van den Bergh

  10. Faculty of Medicine and Life Sciences, University Hasselt, Hasselt, Belgium

    J. P. van den Bergh

  11. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8220, Aarhus N, Denmark

    T. Harsløf, B. Langdahl, S. Gregersen & Jakob Starup-Linde

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  1. Z. Al-Mashhadi
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  6. T. Harsløf
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  7. B. Langdahl
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  9. Jakob Starup-Linde
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Corresponding author

Correspondence to Jakob Starup-Linde.

Ethics declarations

Zheer Al-Mashhadi and Jakob Starup-Linde drafted the manuscript, conducted the systematic literature search contributed to the interpretation of data, critical editing of written text, and approved the final version of the manuscript. Rikke Viggers, Rasmus Fuglsang-Nielsen, Frank de Vries, Joop van den Bergh, Torben Harsløf, Bente Langdahl, and Søren Gregersen contributed to the interpretation of data, critical editing of written text, and approved the final version of the manuscript.

Conflict of Interest

Z Al-Mashhadi, R Viggers, R Fuglsang-Nielsen, JP van den Bergh, T Harsløf and S Gregersen declare no conflict of interest.

J. Starup-Linde reports personal fees from GSK Pharma A/S and Gilead Sciences Denmark, outside the submitted work.

F. de Vries supervises three PhD students who are currently employed with F. Hoffmann La Roche Ltd. (Welwyn Garden City UK and Basel, Switzerland). The topics of their PhDs do not relate to the current study. Dr. de Vries has not received any fees or reimbursements for this.

JP van den Bergh reports grants from Amgen, UCB and Eli-Lilly and personal fees from UCB and Amgen outside the submitted work.

B. Langdahl reports grants from Amgen, grants from Novo Nordisk, personal fees from Amgen, personal fees from UCB, personal fees from Gedeon-Richter, personal fees from Gilead, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

PRISMA flow diagram adapted from From Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:https://doi.org/10.1371/journal.pmed1000097

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This article is part of the Topical Collection on Bone and Diabetes

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Al-Mashhadi, Z., Viggers, R., Fuglsang-Nielsen, R. et al. Glucose-Lowering Drugs and Fracture Risk—a Systematic Review. Curr Osteoporos Rep 18, 737–758 (2020). https://doi.org/10.1007/s11914-020-00638-8

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