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image of Dipeptidyl Peptidase-4 Inhibitors and Risk of Fractures in Type 2 Diabetes Mellitus Patients: A Bayesian Network Meta-Analysis

Abstract

Background/Objective

Type 2 diabetes mellitus (T2DM) contributes to an increased fracture risk and impaired bone health. The impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on bone fracture risk is unclear. We performed a network meta-analysis (NMA) to assess the impact of DPP-4i on fracture risk in patients with T2DM.

Methods

A comprehensive systematic literature search was conducted on PubMed/Medline, Cochrane Library, and ClinicalTrials.gov until June 2024 to identify RCTs reporting fracture events with DPP-4i among T2DM patients. A Bayesian NMA has been performed to calculate the odds ratio (OR) and 95% credible intervals (CrI). Surface under the cumulative ranking analysis (SUCRA) was utilized to assess the rank probability of DPP-4i.

Results

A total of 85 RCTs were identified, including 89,965 T2DM patients with 1,083 fracture events. In the direct meta-analysis, DPP-4i did not elevate fracture risk compared to placebo or other oral anti-diabetics (OADs) (OR (95%CI): 1.04 (0.91-1.18); =0.57 and 1.18 (0.79-1.74); =0.96, respectively). Alogliptin and sitagliptin indicated a non-significant trend towards reducing fracture risk compared to placebo (OR (95%CI): 0.59 (0.31-1.15); =0.12) and OADs (OR (95%CI): 0.73 (0.41-1.30); =0.28), respectively. In the NMA, alogliptin significantly reduced fracture risk compared to linagliptin and SGLT2i (OR (95%CrI): 0.41 (0.16-0.93) and 0.16 (0.017-0.83), respectively). Conversely, linagliptin increased fracture risk compared to sulfonylurea (OR (95%CrI): 2.3 (1.1-5.2). According to SUCRA, alogliptin (84%) ranked as the preferred treatment for reducing fracture risk in T2DM patients.

Conclusion

Overall, DPP-4i was not associated with an increased risk of fractures in patients with T2DM. However, alogliptin demonstrated a reduced risk of fractures when compared to both linagliptin and SGLT2i. Further long-term clinical studies are needed to confirm the present findings.

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2025-07-09
2025-10-18

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Dipeptidyl Peptidase-4 Inhibitors and Risk of Fractures in Type 2 Diabetes Mellitus Patients: A Bayesian Network Meta-Analysis
Bentham Science Publishers ; https://doi.org/10.2174/0127724328373328250624065307
/content/journals/crcep/10.2174/0127724328373328250624065307
/content/journals/crcep/10.2174/0127724328373328250624065307
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  • Article Type:     Research Article
Keywords: Diabetes mellitus ; mixed treatment comparison (MTC) ; bone health ; network meta-analysis (NMA) ; fracture ; type 2 diabetes mellitus

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