Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control

Authors

  • Adriana M. Hung,

    Corresponding author
    1. Clinical Science Research and Development, VA Tennessee Valley, Nashville, TN, USA
    2. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    3. Department of Medicine, Vanderbilt University, Nashville, TN, USA
    • Division of Nephrology, Vanderbilt University, Nashville, TN, USA
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  • Christianne L. Roumie,

    1. Clinical Science Research and Development, VA Tennessee Valley, Nashville, TN, USA
    2. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    3. Department of Medicine, Vanderbilt University, Nashville, TN, USA
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  • Robert A. Greevy,

    1. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    2. Department of Biostatistics, Vanderbilt University, Nashville, TN, USA
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  • Xulei Liu,

    1. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    2. Department of Biostatistics, Vanderbilt University, Nashville, TN, USA
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  • Carlos G. Grijalva,

    1. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    2. Department of Preventive Medicine, Vanderbilt University, Nashville, TN, USA
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  • Harvey J. Murff,

    1. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    2. Department of Medicine, Vanderbilt University, Nashville, TN, USA
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  • Marie R. Griffin

    1. Geriatric Research Education Clinical Center (GRECC), and Health Services Research, and Clinical Research Center of Excellence (CRCoE), VA Tennessee Valley, Nashville, TN, USA
    2. Department of Medicine, Vanderbilt University, Nashville, TN, USA
    3. Department of Preventive Medicine, Vanderbilt University, Nashville, TN, USA
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Correspondence to: A. M. Hung, Division of Nephrology, Vanderbilt University Medical Center, 1161 21st Ave. South & Garland, S-3223 MCN, Nashville, TN 37232, USA. E-mail: Adriana.hung@vanderbilt.edu

ABSTRACT

Background and objective

We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control.

Methods

We identified 13 238 veterans who initiated sulfonylurea or metformin treatment (2000–2007) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/minute, and followed them until a study event occurred, non-persistence on treatment, loss of follow-up, or end of the study. The composite outcome was a sustained decline from baseline eGFR of ≥25%, end-stage renal disease, or death. We estimated the association of cumulative measurements of potential mediators including BMI, SBP, and glycated hemoglobin on the study outcome. We determined if controlling for these time-varying covariates accounted for the differences in outcome between sulfonylurea and metformin initiators.

Results

Compared to sulfonylurea use, metformin use was associated with a lower risk for renal function decline or death [adjusted hazard ratio (aHR) 0.82, 95% confidence interval 0.70, 0.97]. This protective association remained significant [aHR 0.83 (0.70–0.98)] when accounting for the cumulative time-varying measurements of the three mediators of interest.

Conclusion

Metformin initiation was associated with a lower risk of kidney function decline or death compared to sulfonylureas, which appeared to be independent of changes in BMI, SBP, and glycated hemoglobin over time. Copyright © 2013 John Wiley & Sons, Ltd.

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