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Diabetes Care. 2018 Apr;41(4):713-722. doi: 10.2337/dc17-0294. Epub 2018 Feb 2.

Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia.

Author information

1
Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA celeonar@pennmedicine.upenn.edu.
2
Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
3
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, Anschutz Medical Campus, University of Colorado, Aurora, CO.
4
Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
5
Kaiser Permanente Washington Health Research Institute, Seattle, WA.
6
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
7
Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
8
Division of Comparative Effectiveness, Department of Healthcare Policy and Research, Weill Cornell Medical Center, Cornell University, New York, NY.
9
Memorial Sloan Kettering Cancer Center, New York, NY.
10
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
11
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Abstract

OBJECTIVE:

To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA).

RESEARCH DESIGN AND METHODS:

We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model.

RESULTS:

Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null.

CONCLUSIONS:

Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.

PMID:
29437823
PMCID:
PMC5860838
DOI:
10.2337/dc17-0294
[Indexed for MEDLINE]
Free PMC Article

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