Journal
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
Volume 74, Issue 15, Pages 1143-1151Publisher
OXFORD UNIV PRESS INC
DOI: 10.2146/ajhp160319
Keywords
diabetes mellitus; type 2/drug therapy; fractures; bone; hypoglycemic agents; thiazolidinediones; SGLT2 inhibitor
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Purpose. Published data on the risk of bone fractures associated with medications used for the treatment of type 2 diabetes mellitus are summarized. Summary. A systematic literature search identified 108 publications on controlled trials and 6 meta-analyses addressing the potential for fractures with the use of 7 commonly used antidiabetic classes: thiazolidinediones (TZDs), sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, big-uanides, insulin, and sulfonylureas. Among all the classes of agents evaluated, only TZDs have been clearly linked to significantly increased fracture risk (number needed to harm [NNH], 99 in one meta-analysis and 172 in another meta-analysis) and only in female patients. Interim data from an ongoing large placebo-controlled trial suggest that use of the SGLT2 inhibitor canagliflozin may be associated with an elevated rate of fractures (absolute risk increase, 1.4%; NNH, 71) and decreased total-hip bone mineral density. Published data regarding the other evaluated classes of agents generally show no effect on fracture risk; some evidence suggests a small bone-protective effect with the use of DPP-4 inhibitors. Conclusion. In patients with type 2 diabetes mellitus, evidence is strongest that, among antidiabetic drugs, TZDs increase the risk of bone fractures; thus, TZDs should be used with caution in women. Canagliflozin is the only SGLT2 inhibitor linked to an increased fracture rate. Metformin, sulfonylureas, insulin, DPP-4 inhibitors, and GLP-1 agonists appear to have overall neutral effects on bone fractures.
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