Journal of General Internal Medicine

, Volume 33, Issue 2, pp 155–165 | Cite as

Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease

  • Zachary A. Marcum
  • Christopher W. Forsberg
  • Kathryn P. Moore
  • Ian H. de Boer
  • Nicholas L. Smith
  • Edward J. Boyko
  • James S. Floyd



For patients with type 2 diabetes and chronic kidney disease (CKD), high-quality evidence about the relative benefits and harms of oral glucose-lowering drugs is limited.


To evaluate whether mortality risk differs after the initiation of monotherapy with either metformin or a sulfonylurea in Veterans with type 2 diabetes and CKD.


Observational, national cohort study in the Veterans Health Administration (VHA).


Veterans who received care from the VHA for at least 1 year prior to initiating monotherapy treatment for type 2 diabetes with either metformin or a sulfonylurea between 2004 and 2009.

Main Measures

Metformin and sulfonylurea use was assessed from VHA electronic pharmacy records. The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR). The outcome of death from January 1, 2004, through December 31, 2009, was assessed from VHA Vital Status files.

Key Results

Among 175,296 new users of metformin or a sulfonylurea monotherapy, 5121 deaths were observed. In primary analyses adjusted for all measured potential confounding factors, metformin monotherapy was associated with a lower mortality hazard ratio (HR) compared with sulfonylurea monotherapy across all ranges of eGFR evaluated (HR ranging from 0.59 to 0.80). A secondary analysis of mortality risk differences favored metformin across all eGFR ranges; the greatest risk difference was observed in the eGFR category 30–44 mL/min/1.73m2 (12.1 fewer deaths/1000 person-years, 95% CI 5.2–19.0).


Initiation of metformin versus a sulfonylurea among individuals with type 2 diabetes and CKD was associated with a substantial reduction in mortality, in terms of both relative and absolute risk reduction. The largest absolute risk reduction was observed among individuals with moderately–severely reduced eGFR (30–44 mL/min/1.73m2).


diabetes chronic kidney disease mortality 


Funding Source

Dr. Floyd received financial support from the National Heart, Lung, and Blood Institute (NHLBI grant K08HL116640). The views expressed by Drs. Boyko and Smith are theirs alone and do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

Compliance with Ethical Standards

Conflict of Interest

All authors declare that they have no relevant financial interests, activities, relationships, or affiliations, or other potential conflicts of interest to report.


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Copyright information

© Society of General Internal Medicine 2017

Authors and Affiliations

  • Zachary A. Marcum
    • 1
  • Christopher W. Forsberg
    • 2
  • Kathryn P. Moore
    • 2
  • Ian H. de Boer
    • 3
    • 4
    • 5
  • Nicholas L. Smith
    • 2
    • 4
    • 6
    • 7
  • Edward J. Boyko
    • 2
    • 3
    • 8
  • James S. Floyd
    • 3
    • 4
    • 6
    • 7
  1. 1.Department of Pharmacy, School of PharmacyUniversity of WashingtonSeattleUSA
  2. 2.Seattle Epidemiologic Research and Information CenterVA Puget Sound Health Care SystemSeattleUSA
  3. 3.Department of MedicineUniversity of WashingtonSeattleUSA
  4. 4.Department of EpidemiologyUniversity of WashingtonSeattleUSA
  5. 5.Kidney Research InstituteUniversity of WashingtonSeattleUSA
  6. 6.Cardiovascular Health Research UnitUniversity of WashingtonSeattleUSA
  7. 7.Kaiser Permanente Washington Health Research InstituteKaiser Permanente WashingtonSeattleUSA
  8. 8.General Medicine ServiceVA Puget Sound Health Care SystemSeattleUSA

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