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Cited by 31Diabetes Treatment and ManagementDiabetes Management and ResearchChronic Kidney Disease and Diabetes

Hospitalization for lactic acidosis among patients with reduced kidney function treated with metformin or sulfonylureas

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Chu, Patricia Y., Hackstadt, Amber J., Chipman, Jonathan, Griffin, Marie R., Hung, Adriana M., Greevy, Robert A., Grijalva, Carlos G., Elasy, Tom +1 more·2020·Diabetes Care
DOI 10.2337/dc19-2391PMC PMC7305006
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Abstract

OBJECTIVE To compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function. RESEARCH DESIGN AND METHODS This retrospective cohort combined data from the National Veterans Health Administration, Medicare, Medicaid, and the National Death Index. New users of metformin or sulfonylureas were followed from development of reduced kidney function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 or serum creatinine ≥1.4 mg/dL [female] or 1.5 mg/dL [male]) through hospitalization for lactic acidosis, death, loss 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 h of admission). We report the cause-specific hazard of lactic acidosis hospitalization between metformin and sulfonylureas from a propensity score–matched weighted cohort and conduct an additional competing risks analysis to account for treatment change and death. RESULTS The weighted cohort included 24,542 metformin users and 24,662 sulfonylurea users who developed reduced kidney function (median age 70 years, median eGFR 55.8 mL/min/1.73 m2). There were 4.18 (95% CI 3.63, 4.81) vs. 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 [95% CI 0.99, 1.50]). Results were consistent for both primary discharge diagnosis (aHR 1.11 [0.87, 1.44]) and laboratory-confirmed lactic acidosis (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 those patients who continued sulfonylureas.

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Crossref · 10.2337/dc19-2391

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  • The benefits and risks of continuing metformin treatment should be reassessed when eGFR falls to <45 mL/min/1.73m2.

    “3) the benefits and risks of continuing treatment should be reassessed when eGFR falls to <45 mL/min/1.73m 2 (104,105)”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [105]

    The Conclusions discuss guidance to continue metformin at reduced eGFR, and the Results (Sensitivity and Subgroup Analysis; page unavailable) examine patients with eGFR <45 mL/min/1.73 m². The paper does not say that the benefits and risks of continuing treatment should be reassessed at that threshold. (LLM, conf=0.76)

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  • eGFR should be monitored while taking metformin.

    “2) eGFR should be monitored while taking metformin”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [105]

  • Metformin is contraindicated in individuals with an eGFR <30 mL/min/1.73m2.

    “1) metformin is contraindicated in individuals with an eGFR <30 mL/min/1.73m 2”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [105]

  • Metformin should not be initiated for individuals with an eGFR <45 mL/min/1.73m2.

    “4) metformin should not be initiated for individuals with an eGFR <45 mL/min/1.73m 2”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [105]

    The Introduction describes an FDA contraindication at eGFR <30 mL/min/1.73 m², while the study examines continued metformin use rather than starting treatment. The Conclusions discuss guidance on continuation at reduced eGFR. Neither passage states whether metformin should be initiated below 45 mL/min/1.73 m²; searches for initiation and that threshold found no such recommendation. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • Metformin should be temporarily discontinued at the time of or before iodinated contrast imaging procedures in individuals with eGFR 30-60 mL/min/1.73m2.

    “5) metformin should be temporarily discontinued at the time of or before iodinated contrast imaging procedures in individuals with eGFR 30-60 mL/min/1.73m 2 .”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [105]

    The Introduction and Conclusions discuss metformin use at reduced eGFR, but neither addresses iodinated contrast imaging or temporary discontinuation around a procedure. Searches for iodinated contrast and for holding metformin before imaging found no passage supporting that specific recommendation; page numbers were not available in our copy. (LLM, conf=0.72)

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Research works printed but not linked: 1

  1. [22]Executive Committee KDIGO clinical practice guideline on diabetes management in chronic kidney disease [Internet]. Available from https://kdigo.org/wp-content/uploads/2018/03/KDIGO-Diabetes-Management-in-CKD_Public-Review.pdf. Accessed 12 February 2020

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Authors
Chu, P. Y., Hackstadt, A. J., Chipman, J., Griffin, M. R., Hung, A. M., Greevy, R. A., Grijalva, C. G., Elasy, T., & Roumie, C. L.
Affiliations
  • Veterans Health Administration (US)
  • Vanderbilt University (US)
  • University of Utah (US)
Corresponding author
Roumie, Christianne L.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2020-04-23
Volume
43
Issue
7
Pages
1462-1470
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc19-2391
PMC
PMC7305006
OpenAlex
W3019600263
Cited by
31
References
26
Citations by year
2026: 1 · 2025: 6 · 2024: 1 · 2023: 3 · 2022: 10 · 2021: 5 · 2020: 5
FWCI
4.34
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/content/license (vor, 57 d)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (Center for Diabetes Translation Research P30-DK-092986)
  • Office of Research and Development (CX000570-07)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
lactic acidosis, metformin, sulfonylureas, reduced renal function, chronic kidney disease, diabetes mellitus, veterans, hospitalization risk, drug safety, competing risks
MeSH terms
Acidosis, Lactic, Aged, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Hospitalization, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Retrospective Studies, Sulfonylurea Compounds, United States, Veterans, Cohort Studies, Renal Insufficiency

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