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Hospitalization for Lactic Acidosis among Patients with Reduced Kidney Function treated with Metformin or Sulfonylureas

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posted on 04.06.2020 by Patricia Y. Chu, Amber J. Hackstadt, Jonathan Chipman, Marie R. Griffin, Adriana M. Hung, Robert A. Greevy, Jr., Carlos G. Grijalva, Tom Elasy, Christianne L. Roumie
Objective: Compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylurea following development of reduced kidney function.

Research Design and Methods: This retrospective cohort combined data from National Veterans Health Administration, Medicare, Medicaid and National Death Index. New users of metformin or sulfonylurea were followed from development of reduced kidney function (estimated Glomerular Filtration Rate [eGFR] <60 ml/min or serum creatinine >1.4 [female] or 1.5 [male] mg/dL) through hospitalization for lactic acidosis, death, lost to follow-up or study end. Lactic acidosis hospitalization was defined as a composite of primary discharge diagnosis or laboratory-confirmed lactic acidosis (lactic acid >2.5 mmol/L and either arterial blood pH <7.35 or serum bicarbonate <19 mmol/L within 24 hours of admission). We report the cause specific hazard of lactic acidosis hospitalization between metformin and sulfonylurea from a propensity score matched weighted cohort, and conduct additional competing risks analysis to account for treatment change and death.

Results: The weighted cohort included 24,542 metformin and 24,662 sulfonylurea users who developed reduced kidney function (median age 70 years, median eGFR 55.8 ml/min/1.73m2). There were 4.18 [3.63, 4.81] versus 3.69 [3.19, 4.27] lactic acidosis hospitalizations per 1,000 person-years among metformin and sulfonylurea users, respectively (adjusted hazard ratio (aHR) 1.21 [0.99, 1.50]). Results were consistent for both primary discharge diagnosis (aHR 1.11 [0.87, 1.44]) and laboratory-confirmed lactic acidosis (aHR 1.25 [0.92,1.70]).

Conclusions: Among veterans with diabetes who developed reduced kidney function, occurrence of lactic acidosis hospitalization was uncommon and not statistically different between patients who continued metformin and sulfonylurea.

Funding

This project was funded by the by VA Clinical Science research and Development investigator-initiated grant CX000570-07 (Roumie). Drs. Chu, Roumie, Hackstadt and Elasy were supported in part by Center for Diabetes Translation Research P30DK092986. Support for Veterans Affairs/Centers for Medicare & Medicaid Services data provided by the Department of Veterans Affairs, Veterans Affairs Health Services Research and Development Service, Veterans Affairs Information Resource Center (project numbers SDR 02-237 and 98-004). The VA Clinical Science Research and Development had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

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