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ADA: Sulfonylureas Along with TZDs May Increase Risk for Fractures in Diabetes

A large database analysis has found that two oral diabetes drug classes, thiazolidinediones (TZDs) and sulfonylureas, both increase the risk for fractures when compared with metformin…. 

Sandhya Mehta, PhD, an investigator, along with Inovalon, a technology company that specializes in large data analytics, spoke at the 2014 ADA Scientific Sessions regarding an observational study that confirmed the previous findings of the risk of increased fractures associated with TZDs but is the first to suggest a possible increased fracture risk with sulfonylureas. Dr. Mehta stated when it comes to patients who are already at a higher risk for fractures her study’s findings should be taken into consideration.

A longitudinal retrospective cohort study using a large administrative claims database was conducted to examine the comparative safety in regards to risk fractures of antidiabetic medications. Dr. Mehta and colleagues analyzed 2009-2012 data from Invalon’s Medical Outcomes for Effectiveness and Economics (MORE) registry of more than 100 million individuals. A total of 99,892 adults were identified as new users of glucose-lowering medications. Of those, 77.8% were on metformin, 15.3% on sulfonylureas, 2.7% on dipeptidyl peptidase-4 inhibitors (DPP-4), 2.7% on thiazolidinediones (TZDs), 0.81% on incretins, and 0.6% on meglitinides. Following a five-year follow-up period, out of the 99,892 patients, 7,353, which was 7.4%, had evidence of a fracture. Among the total 76,924 patients taking metformin 6.8% had an incidence of fractures, among the 2,679 patients taking TZDs, 10.9% had fractures, and out of the 15,162 patients taking sulfonylureas, 9.7% had fractures. Additionally, those taking other glucose-lowering agents such as incretin drugs, 799 patients, 10.9% had fractures, and 626 patients on meglitinides 10.7% had fractures.

After adjustments such as age, gender, region, and variety of medical conditions and other medications were made, the hazard ratio for fracture risk when compared with metformin was 1.40 for TZDs (P<0.0001), and 1.09 for sulfonylureas (P=0.0054). The other glucose-lowering agents when compared with metformin did not reach statistical significance. The study found that the risk for fractures is nine to forty percent higher in patients taking sulfonylureas and TZDs. Therefore, according to Dr. Mehta’s presentation, the findings support the hypothesis which stated TZDs increase fracture risk by decreasing bone-mineral density, inhibiting osteoclast differentiation, and stimulating adipocytes. However, she noted previous epidemiologic studies have failed to find an increased fracture risk with sulfonylureas. This suggests that further investigation on the association between sulfonylureas and the risk for increased fractures needs to be done.

Practice Pearls:
  • Among the 2,679 patients taking TZDs, 10.9% had fractures
  • Out of the 15,162 patients taking sulfonylureas, 9.7% had fractures.
  • The study found that the risk for fractures is nine to forty percent higher in patients taking sulfonylureas and TZDs.
  • However, previous epidemiologic studies have failed to find an increased fracture risk with sulfonylureas and this suggests that further investigation on the association between sulfonylureas and the risk for increased fractures needs to be done.

Presented at the American Diabetes Association’s 74th Scientific Sessions, June, 2014 – 165-OR – Comparative Safety of Oral Antidiabetic Therapy on Risk of Fracture in Patients with Diabetes