Comparative Safety of Oral Antidiabetic Therapy on Risk of Fracture in Patients with Diabetes

Some clinical and observational studies suggest that the use of antidiabetic drug classes such as thiazolidinediones (TZD) can increase the risk of fracture in patients with Diabetes. However, no studies have examined the long term risk across all classes of anti-diabetic drug therapies with respect to fracture incidence. A longitudinal retrospective cohort study using a large administrative claims database was conducted to examine the comparative safety of antidiabetics_sulfonylureas, biguanides (metformin), incretin mimetic agents, meglitinide analogues, TZD, and dipeptidyl peptidase-4 inhibitors (DPP-4)_on risk of fracture.

Patients were included in the cohort if they met the following criteria: ≥18 years old, new users of antidiabetic drugs, diagnosis of diabetes before initiating treatment, continuously enrolled for 12-months before and at least 12-months after initiation of treatment, no diagnosis of fracture in 12-months before treatment, and not prescribed more than one antidiabetic drug class.

Multivariate survival analysis was performed. Patients were censored at the time of event, at disenrollment or at the end of follow-up period. A total of 99,892 adults (metformin (77.8%), sulfonylureas (15.3%), DPP4 (2.7%), TZD (2.7%), incretins (0.81%), and meglitinides (0.6%)) were identified as new users of antidiabetic drugs. Within the 5 year follow-up period, 7,353 patients (7.4%) had evidence of fracture. After adjusting for potential confounders, a significantly higher risk of fracture was found in users of sulfonylureas (HR 1.09, 95% CI 1.03-1.16) and TZD (HR 1.40, 95% CI 1.25-1.58) as compared to metformin. No statistical difference was found between metformin and other antidiabetic drug classes. This large longitudinal study found that risk of fracture is 9 to 40 percent higher in users of sulfonylureas and TZD.

These findings should be taken into consideration in prescribing antidiabetic drugs, especially in those patients already at higher risk for fracture.

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And it appears we are more susceptible to fractures so adding theses drugs is only going to exacerbate the the risk.

Risk for fracture, post-fracture complications higher in diabetes

Patients with diabetes are at an increased long-term risk for fracture and more prone to adverse events and death after a fracture, according to recent findings.

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Graham