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A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study

  • Reid H. Whitlock
    Affiliations
    Seven Oaks General Hospital, Chronic Disease Innovation Centre, Winnipeg, MB, Canada
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  • Ingrid Hougen
    Affiliations
    Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
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  • Paul Komenda
    Affiliations
    Seven Oaks General Hospital, Chronic Disease Innovation Centre, Winnipeg, MB, Canada

    Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
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  • Claudio Rigatto
    Affiliations
    Seven Oaks General Hospital, Chronic Disease Innovation Centre, Winnipeg, MB, Canada

    Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
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  • Kristin K. Clemens
    Affiliations
    Institute of Clinical Evaluative Sciences, London, ON, Canada

    Division of Endocrinology, Department of Medicine, London, ON, Canada

    Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

    St. Joseph’s Health Care London, London, ON, Canada

    Lawson Health Research Institute, London, ON, Canada
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  • Navdeep Tangri
    Correspondence
    Correspondence: Address to Navdeep Tangri, MD, PhD, Seven Oaks General Hospital, 2LB19-2300 McPhillips St, Winnipeg, MB R2V 3M3, Canada.
    Affiliations
    Seven Oaks General Hospital, Chronic Disease Innovation Centre, Winnipeg, MB, Canada

    Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
    Search for articles by this author

      Abstract

      Objective

      To compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage.

      Patients and Methods

      This retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m2. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome.

      Results

      The cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes.

      Conclusion

      Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD.

      Abbreviations and Acronyms:

      CKD (chronic kidney disease), eGFR (estimated glomerular filtration rate), HR (hazard ratio), IPTW (inverse probability of treatment weight), IQR (interquartile range), OHA (oral antihyperglycemic agent), SMD (standardized mean difference), T2D (type 2 diabetes)
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