Evaluation of the risk of fracture in type 2 diabetes mellitus patients with incretins: an updated meta-analysis

Introduction: The effect of incretins including dipeptidyl peptidase 4 inhibitors (DPP4-Is) and glucagon-like peptide 1 receptor agonists (GLP1-ras) in the treatment of type 2 diabetes increasing the risk of fracture remains controversial. No meta-analysis has been written to discuss this from the prospective interventional studies. The objective was to evaluate the association between the use of incretins and fracture risk. Material and methods: Multiple databases were searched for original articles that investigated the relationship between the use of incretin agents and fracture risk, up to December 2019. Trials using the Mantel-Haenszel method to calculate OR and 95% CI were pooled. The multiple sensitivity, heterogeneity, publication bias, and quality were analysed among the studies to evaluate the robustness of results. Results: The fixed-effects model was used on account of the I-2 test for heterogeneity (I-2 = 0.0%). Incretins were not associated with fracture risk [0.97 (95% CI: 0.88-1.08)]. But in the subgroup analysis, when sitagliptin 100 mg per day (OR 0.495, 95% CI: 0.304-0.806) or liraglutide 1.8 mg per day was administered (OR 0.621, 95% CI: 0.413-0.933), it reduced fracture risk. The sensitivity analysis and publication bias prompted the robustness of results. Conclusions: This meta-analysis suggested that the current use of incretins not only is safe for fracture in type 2 diabetes patients from RCT studies, but also, when sitagliptin 100 mg or liraglutide 1.8 mg per day was administered, it may exhibit protective effects on bone metabolism.

Automated summary

This meta-analysis suggests that the current use of incretins is not associated with increased risk of fracture in type 2 diabetes patients, and in some cases, such as when taking sitagliptin 100 mg or liraglutide 1.8 mg per day, it may even reduce fracture risk.