Zachary A Marcum1, Christopher W Forsberg2, Kathryn P Moore2, Ian H de Boer3,4,5, Nicholas L Smith2,4,6,7, Edward J Boyko2,3,8, James S Floyd9,10,11,12. 1. Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA. 2. Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, WA, USA. 3. Department of Medicine, University of Washington, Seattle, WA, USA. 4. Department of Epidemiology, University of Washington, Seattle, WA, USA. 5. Kidney Research Institute, University of Washington, Seattle, WA, USA. 6. Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA. 7. Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA. 8. General Medicine Service, VA Puget Sound Health Care System, Seattle, WA, USA. 9. Department of Medicine, University of Washington, Seattle, WA, USA. jfloyd@uw.edu. 10. Department of Epidemiology, University of Washington, Seattle, WA, USA. jfloyd@uw.edu. 11. Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA. jfloyd@uw.edu. 12. Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA. jfloyd@uw.edu.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. DESIGN: Observational, national cohort study in the Veterans Health Administration (VHA). PARTICIPANTS: 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). CONCLUSIONS: 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).
BACKGROUND: 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. OBJECTIVE: 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. DESIGN: Observational, national cohort study in the Veterans Health Administration (VHA). PARTICIPANTS: 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). CONCLUSIONS: 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).
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