Current guidance advises against the use of metformin for individuals with advanced kidney disease. However, supporting evidence for this recommendation is lacking. Emilie J. Lambourg, PharmD, PhD, and colleagues conducted an observational cohort study to address this knowledge gap.
Their research included all adults in Scotland with type 2 diabetes (T2D) and incident stage 4 chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) who received metformin treatment between January 2010 and April 2019. The study compared outcomes for patients with T2D who continued metformin treatment with outcomes for patients who stopped treatment with metformin after developing stage 4 CKD. The primary study outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACE). The study followed a target trial emulation framework with a clone-censor-weight design and marginal structural models fit for sensitivity analyses.
A total of 4,278 patients with a T2D diagnosis before April 30, 2019, were identified as prevalent metformin users with incident stage 4 CKD. Within 6 months of reaching stage 4 CKD, 1,713 (40.1%) patients discontinued metformin use. Compared with those who continued using metformin, those who stopped had 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). However, the incidence of MACE was comparable between the 2 groups (HR, 1.05; 95% CI, 0.88-1.26). The results regarding all-cause mortality (HR, 1.34; 95% CI, 1.08-1.67) and incidence of MACE (HR, 1.04; 95% CI, 0.81-1.33) were confirmed by marginal structural models.
Although they cited residual confounding as a limitation, the study’s authors concluded that continuing metformin may be appropriate when a patient’s eGFR falls below 30 mL/min/1.73 m2.
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