EClinicalMedicine (May 2024)
Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation studyResearch in context
Abstract
Summary: Background: Current labelling advises discontinuation of metformin when estimated glomerular filtration rate (eGFR) 5.0 mmol/L with a concomitant blood pH < 7.35 or ICD-9 codes of 276.2) in discontinued-metformin versus continued-metformin users was assessed in a separate register-based cohort. Findings: A total of 33,586 metformin users with new-onset eGFR < 30 ml/min/1.73 m2 were included in the study, 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. During a median follow-up of 3.8 (IQR: 2.2–6.1) years, 16.4% (5505/33,586), 30.1% (10,113/33,586), and 7.1% (2171/30,682) had incident MACE, ESKD, and cancer respectively, and 44.4% (14,917/33,586) died. Compared to continued-metformin use, discontinuation was associated with higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29–1.52), ESKD (HR = 1.52, 1.42–1.62), and death (HR = 1.22, 1.18–1.27). No association was observed for cancer (HR = 0.93, 0.85–1.01). Discontinued-metformin users had higher change in HbA1c change at 6-month of follow-up versus continued-metformin users (weighted mean HbA1c level change: 0.5% [0.4–0.6%] versus 0.2% [0.1–0.2]). In the separate register-based cohort (n = 3235), null association was observed between metformin use and risk of lactic acidosis (weighted HR = 0.94 [0.53–1.64]). Interpretation: Our results suggest that discontinuation of metformin in patients with T2D and chronic kidney disease may be associated with increased risk of cardiovascular-renal events. Use of metformin below eGFR of 30 ml/min/1.73 m2 may be associated with cardiovascular, renal, and mortality benefits that need to be weighed against the risk of lactic acidosis, but further research is needed to validate these findings. Funding: CUHK Impact Research Fellowship Scheme.
