Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study
Abstract
RATIONALE & OBJECTIVE: Despite a lack of supporting evidence, current guidance recommends against the use of metformin in people with advanced kidney impairment. This observational study compared the outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR]<30mL/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 6 months following incident stage 4 CKD.
OUTCOME: 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 April 30, 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within 6 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, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]), and the incidence of MACE was similar between both…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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