SGLT2 Inhibitors and Fracture Risk: A Review of What We Know

March 30, 2015

It's probably too early to pass judgment but data from clinical trials point to decreased bone mineral density and increased treatment-emergent fractures in patients taking the new antidiabetes drugs.

The sodium glucose co-transporter 2 inhibitors lower A1c in a non-insulin dependent manner, are associated with modest weight loss, and have a mild effect on hypertension. Analysis of clinical trial data, however, has found evidence of decreased bone mineral density and of increased bone turnover in patients taking both canagliflozin and dapagliflozin.It remains unclear whether persons with diabetes have coexisting bone disease that may make them more susceptible to adverse effects of the drugs on bone or if the SGLT2 inhibitor mechanism itself underlies the observed changes.  This short slide show summarizes the current literature. 

References:

1. Taylor SI, Blau JE, Rother KI.  Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. Published online December 16, 2014.  http://dx.doi.org/10.1016/S2213-8587(14)70227-X

2. Kahn SE, Zinman B, Lachin JM, et al Diabetes Outcome Progression Trial (ADOPT) Study Group. Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care. 2008;31:845-51. doi: 10.2337/dc07-2270. Epub 2008 Jan 25. http://www.ncbi.nlm.nih.gov/pubmed/?term=10.2337%2Fdc07-2270

3. Kwon H. CANA: clinical efficacy and safety.  Endocrinology and Metabolic Drugs Advisory Committee Meeting, 2013. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM336234.pdf

4. Bode B, Stenlof K, Harris S. Long-term efficacy and safety of CANA over 104 weeks in patients aged 55 to 80 years with type 2 diabetes. Diabetes Obes Metab. 2014 Dec 13. doi: 10.1111/dom.12428. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1111%2Fdom.12428

5. Kohan DE, Fioretto P2, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that DAPA reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014 Apr;85(4):962-71. doi: 10.1038/ki.2013.356. Epub 2013 Sep 25. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973038/