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Sulfonylureas up overall mortality risk
HOUSTON — Commonly prescribed sulfonylureas appear to heighten risk for death in patients with diabetes when compared with metformin. Glipizide and glyburide may be particularly dangerous in diabetes patients with coronary artery disease.
“In the past, these medications were largely considered comparable to one another in terms of their effectiveness and safety. However, recent research has suggested that some sulfonylureas may be safer than others,” Kevin M. Pantalone, DO, of the Summa Western Reserve Hospital in Ohio, said during a presentation here.
Mortality risk
These findings led researchers to conduct a study comparing sulfonylureas to metformin, which is considered to be the preferred first-line treatment for patients with type 2 diabetes, Pantalone said.
Pantalone and colleagues from Cleveland Clinic designed a retrospective cohort study using an electronic health record (EHR) system to identify 23,915 patients with type 2 diabetes.
Of those patients, 12,774 initiated monotherapy with metformin, 4,325 patients with glipizide (Glucotrol, Pfizer), 4,279 with glyburide, and 2,537 with glimepiride (Amaryl, Sanofi-Aventis). Patients aged older than 18 years with and without a history of CAD were included in the study. At baseline, mean age was 61.8 years for the entire cohort and 67.8 years in the subgroup of patients with CAD.
Researchers followed patients for mortality using the EHR and Social Security Death Index.
The median follow-up was 2.2 years. Pantalone said 2,546 deaths occurred during 58,513 person-years of follow-up in the entire cohort, with 419 deaths occurring during 5,980 person-years of follow-up in the subgroup of patients with CAD (n=2,721).
In the entire cohort, results revealed an increase in overall mortality risk with glipizide (HR=1.64; 95% CI, 1.39-1.94), glyburide (HR=1.59; 95% CI, 1.35-1.88) and glimepiride (HR=1.68; 95% CI, 1.37-2.06) as compared with metformin.
However, in patients with CAD, data suggested a significant increase in overall mortality risk with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) vs. metformin, but not with glimepiride.
“Our findings are important because many patients with type 2 diabetes also have coronary artery disease or are at risk for developing coronary artery disease. Thus, our results could potentially impact the care of a large number of patients. All drugs have risks; even those which are generic and cheap. This needs to be taken into consideration by both patients and physicians,” Pantalone said.
Clinical implications
Pantalone concluded that glipizide, glyburide and glimepiride are all associated with an increased risk of overall mortality when compared with metformin.
“Thus, metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes if one has a choice between a sulfonylurea and metformin. However, our results suggested that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred agent in those who have documented coronary artery disease,” Pantalone said.
Pantalone said a prospective study is needed to determine causality.
For more information:
Pantalone KM. Abstract #OR17-4. Presented at: the Endocrine Society’s 94th Annual Meeting & Expo; June 23-26, 2012; Houston.
Disclosure: This research was supported through a grant from Astra Zeneca. Dr. Pantalone reports being a speaker bureau member for Amylin Pharmaceuticals, Inc. Robert S. Zimmerman reports being a speaker bureau member for Novo Nordisk and Santarus, Inc., and is a consultant for Bristol-Myers Squibb and Astra Zeneca. Dr. Zimmerman has also received research funding from Merck & Co. Dr. Michael W Kattan reports being a consultant for Merck & Co., Pfizer, Dendreon and Caris Life Sciences. All other researchers report no relevant financial disclosures.