Daniel Wolverton1, Melissa M Blair2. 1. Graduate Medical Education, Charleston Area Medical Center, Charleston, WV. 2. Department of Pharmacy, New Hanover Regional Medical Center, Wilmington, NC melissa.blair@nhrmc.org.
Abstract
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, biguanides, 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.
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, biguanides, 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.
Authors: Alexander J Eckert; Julia K Mader; Marcus Altmeier; Steffen Mühldorfer; Anton Gillessen; Dhayana Dallmeier; Viral N Shah; Christoph Heyer; Bettina Hartmann; Reinhard W Holl Journal: J Diabetes Complications Date: 2020-06-27 Impact factor: 2.852