Physician-authored summaries and commentary on the most important medical research, provided by the NEJM Group, a division of the Massachusetts Medical Society.
© Massachusetts Medical SocietyMay 2025
Diabetic patients with eGFRs below 30mL/min/1.73m2 who continued metformin had lower mortality at three years.
Metformin is excreted renally and is contraindicated (according to US prescribing information) in patients with estimated glomerular filtration rates (eGFRs) below 30mL/min/1.73m2 to prevent lactic acidosis. However, some evidence suggests that continuing metformin below this eGFR threshold is safe and beneficial. Researchers analysed a Scottish national database of patients with diabetes to identify those taking metformin whose chronic kidney disease progressed to stage 4 or 5 (eGFR, below 30mL/min/1.73m2) and who then either continued metformin for six or more months (about 2600 patients) or discontinued it (about 1700 patients). The researchers used a target-trial emulation study design, which can reduce – but not eliminate – residual confounding.
In adjusted analyses, stopping metformin was associated with higher three-year all-cause mortality (hazard ratio, 1.23); 63% survived among those who stopped metformin, and 70% among continuers. The leading causes of death were cardiovascular events (34%), cancer (17%) and respiratory diseases (10%). The incidence of major adverse cardiovascular events did not differ between groups, but significantly fewer respiratory deaths occurred in metformin continuers. About half of the patients who continued metformin during the study period eventually stopped.
Comment: These results are surprising in two ways. First, many physicians continued patients on metformin despite eGFRs below 30mL/min/1.73m2; second, the survival benefit was not driven by cardiovascular causes. Another recent study also points to a survival benefit for continuing metformin in these patients (eClinicalMedicine 2024; 71: 102568). A compromise might be to continue metformin at lower doses when eGFR fluctuates near 30mL/min/1.73m2 but to discontinue it when eGFR persists below this threshold. These cases should involve shared decision-making with patients.
David S. Weisman, DO, FACP, Associate Professor of Medicine Clinician Educator, Georgetown University Medical Center, Washington, DC; Associate Program Director in Internal Medicine, MedStar Health, Baltimore, USA.
Lambourg EJ, et al. Stopping versus continuing metformin in patients with advanced CKD: a nationwide Scottish target trial emulation study. Am J Kidney Dis 2025; 85: 196-204.e1.
This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.