[OR17-4] Increased Risk of Overall Mortality in Patients with Type 2 Diabetes Receiving Glipizide, Glyburide, and Glimepiride vs. Metformin. A Retrospective Analysis

Kevin M Pantalone, Michael W Kattan, Changhong Yu, Brian J Wells, Susana Arrigain, Anil Jain, Ashish Atreja, Robert S Zimmerman. Summa Western Reserve Hospital Physicians, Inc, Hudson, OH; Cleveland Clinic, Cleveland, OH; Cleveland Clinic, Cleveland, OH; Cleveland Clinic, Cleveland, OH; Cleveland Clinic, Cleveland, OH.

Background: It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). Conflicting reports have surfaced concerning whether an increased overall mortality (or cardiovascular mortality) risk accompanies the various sulfonylureas (1-6). A difference in mortality risk may exist, as the individual sulfonylureas vary significantly from one another in terms of hypoglycemic risk, sulfonylurea receptor selectivity, and their effects on myocardial ischemic preconditioning (7, 8).
Purpose: To assess the risk of overall mortality in patients with type 2 diabetes treated with glipizide, glyburide, or glimepiride vs. metformin.
Methods: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 23,915 patients with type 2 diabetes who initiated monotherapy with metformin (N=12,774), glipizide (N=4,325), glyburide (N=4,279), or glimepiride (N=2,537), ≥ 18 years of age, with and without a history of CAD. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare the anti-diabetic monotherapies.
Results: Baseline characteristics for the entire cohort and subgroup of patients with CAD include mean age (years) +/- SD of 61.8 +/- 14.3 and 67.9 +/- 11.0 years, 50.4% and 69% male, and 77.9% and 84% Caucasian, respectively. The median follow-up was 2.2 years. There were a total of 2,546 deaths in 58,513 person years of follow-up in the entire cohort, and 419 deaths in 5,980 person years of follow-up in the subgroup of patients with documented CAD. An increase in overall mortality risk was observed in the entire cohort 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) vs. metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) vs. metformin.
Conclusions: Glipizide, glyburide, and glimepiride are associated with an increased risk of overall mortality vs. metformin. Our results suggest that if a sulfonylurea is required to obtain glycemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD.

1. Khalangot M et al.,Diabetes Res Clin Pract 2009 Dec;86(3):247-53. 2. Pantalone KM et al.,Diabetes Care 2010 Jun;33(6):1224-1229. 3. Schramm TK et al., Eur Heart J. 2011 Aug;32(15):1900-8. 4. Zeller M et al., J Clin Endocrinol Metab. 2010 Nov;95(11):4993-5002. 5. Horsdal HT et al., Diabetes Metab Res Rev 2009 Sep;25(6):515-522. 6. Andersson C et al., Diabetes Res Clin Pract 2011 Oct;94(1):119-125. 7. Gangji AS et al., Diabetes Care 2007 Feb;30(2):389-394. 8. Krentz AJ., International Congress Series 2003;1253:261-277.

Sources of Research Support: This research was supported through a grant from Astra Zeneca.

Disclosures: RSZ: Speaker Bureau Member, Novo Nordisk, Santarus, Inc.; Consultant, Bristol-Myers Squibb, Astra Zeneca; Research Funding, Merck & Co. Nothing to Disclose: KMP, MWK, CY, BJW, SA, AJ, AA

Date: Sunday, June 24, 2012
Session Info: ORAL SESSION: Emerging Strategies in Diabetes (11:15 AM-12:45 PM)
Presentation Time: 12:00 pm
Room: Theater C

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