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

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.