Effects of incretin-related diabetes drugs on bone formation and bone resorption

Hideki Kitaura, Saika Ogawa, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Adya Pramusita, Ria Kinjo, Jinghan Ma, Kayoko Kanou, Itaru Mizoguchi

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)


Patients with type 2 diabetes have an increased risk of fracture compared to the general population. Glucose absorption is accelerated by incretin hormones, which induce insulin secretion from the pancreas. The level of the incretin hormone, glucagon-like peptide-1 (GLP-1), shows an immediate postprandial increase, and the circulating level of intact GLP-1 is reduced rapidly by dipeptidyl peptidase-4 (DPP-4)-mediated inactivation. Therefore, GLP-1 receptor agonists and DPP-4 inhibitors are effective in the treatment of type 2 diabetes. However, these incretin-related diabetic agents have been reported to affect bone metabolism, including bone formation and resorption. These agents enhance the expression of bone markers, and have been applied to improve bone quality and bone density. In addition, they have been reported to suppress chronic inflammation and reduce the levels of inflammatory cytokine expression. Previously, we reported that these incretin-related agents inhibited both the expression of inflammatory cytokines and inflammation-induced bone resorption. This review presents an overview of current knowledge regarding the effects of incretin-related diabetes drugs on osteoblast differentiation and bone formation as well as osteoclast differentiation and bone resorption. The mechanisms by which incretin-related diabetes drugs regulate bone formation and bone resorption are also discussed.

Original languageEnglish
Article number6578
JournalInternational Journal of Molecular Sciences
Issue number12
Publication statusPublished - 2021 Jun 2


  • Diabetes
  • DPP-4
  • DPP-4 inhibitor
  • GLP-1
  • GLP-1 receptor agonist
  • Osteoblast
  • Osteoclast


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