Emilie J Lambourg, Edouard L Fu, Stuart McGurnaghan, Bryan R Conway, Neeraj Dhaun, Christopher H Grant, Ewan R Pearson, Patrick B Mark, John Petrie, Helen Colhoun, Samira Bell
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引用次数: 0
Abstract
Rationale & objective: Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of supporting evidence. The aim of this observational study was to compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (eGFR <30 ml/min/1.73m2).
Study design: Nationwide observational cohort study.
Setting & participants: All adults with type 2 diabetes and incident stage 4 CKD in Scotland who were treated with metformin between January 2010 and April 2019.
Exposure: Stopping versus continuing metformin within six months following incident stage 4 CKD.
Outcomes: Primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE).
Analytical approach: Target trial emulation with clone-censor-weight design and marginal structural models fit for sensitivity analyses.
Results: In a population of 371,742 Scottish residents with a diagnosis of type 2 diabetes before 30th April 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within six months of developing CKD stage IV, 1,713 (40.1%) individuals discontinued metformin. Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7%, 95% CI 60.9 to 66.6 versus 70.5%, 95% CI 68.0 to 73.0; HR=1.26, 95% CI 1.10 to 1.44), while the incidence of MACE was similar between both strategies (HR=1.05, 95% CI 0.88 to 1.26). Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR=1.34, 95% CI 1.08 to 1.67; MACE: HR=1.04, 95% CI 0.81 to 1.33).
Limitations: Residual confounding.
Conclusions: The continued use of metformin may be appropriate when eGFR falls below 30 ml/min/1.73m2. Randomized controlled trials are needed to confirm these findings.
期刊介绍：
The American Journal of Kidney Diseases (AJKD), the National Kidney Foundation's official journal, is globally recognized for its leadership in clinical nephrology content. Monthly, AJKD publishes original investigations on kidney diseases, hypertension, dialysis therapies, and kidney transplantation. Rigorous peer-review, statistical scrutiny, and a structured format characterize the publication process. Each issue includes case reports unveiling new diseases and potential therapeutic strategies.
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