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 peptide1 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 I² test for heterogeneity (I² = 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.