Compared with linagliptin and saxagliptin, the dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin is associated with a lower risk for bone fracture in patients with type 2 diabetes, according to findings from a meta-analysis published in PLoS One.

A total of 75 randomized controlled trials comparing DPP-4 inhibitors with placebo or other anti-diabetic medications in 70,207 patients with type 2 diabetes were identified and included in this meta-analysis. Included studies had a duration of >12 weeks and reported bone fracture incidence.

Studies compared alogliptin, linagliptin, saxagliptin, sitagliptin, or vildagliptin to controls (placebo, sulfonylureas, glucagon-like peptide-1 receptor agonists, metformin, thiazolidinediones, or sodium-glucose co-transporter 2 inhibitors).

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Compared with placebo, patients taking alogliptin experienced a greater risk reduction in terms of fracture (odds ratio [OR], 0.51; 95% CI, 0.29 to 0.88). In addition, alogliptin demonstrated a lower risk for fracture compared with saxagliptin (OR, 0.46; 95% CI, 0.25 to 0.84) and linagliptin (OR, 0.45; 95% CI, 0.20 to 0.99). 

Overall, patients taking saxagliptin had a higher risk for bone fracture than patients taking sulfonylureas (OR, 1.98; 95% CI, 1.06 to 3.71) and sitagliptin (OR, 1.90; 95% CI, 1.04 to 3.47).

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The small number of trials in the included literature reporting the association between DPP-4 inhibitors and fracture risk represents a potential limitation of the findings. 

In addition, some of the trials included in this meta-analysis had short follow-up periods, which prevented the researchers from determining the long-term impact of these medications on fracture risk.

The results of this study may aid in the “proper prescription for patients in different conditions” and supports the notion that therapeutic decisions should be made carefully in patients with diabetes at risk for fractures.


Yang J, Huang C, Wu S, et al. The effects of dipeptidyl peptidase-4 inhibitors on bone fracture among patients with type 2 diabetes mellitus: A network meta-analysis of randomized controlled trials. PLoS One. 2017;12:e0187537.

This article originally appeared on Endocrinology Advisor