Abstract
Introduction: Metformin can now be used in patients with chronic kidney disease (CKD) up to estimated glomerular filtration rate [eGFR] ≥30 ml/min/1.73m2. However, surveys suggested its continuing use in some patients with eGFR<30 ml/min/1.73m2 in real world practice although the risk-benefit ratios remain uncertain. Methods: This was a prospective, population-based cohort of 36,940 patients with diabetes in Hong Kong stratified by continuation of metformin within 6 months after reaching eGFR<30 ml/min/1.73m2 in 2002-2018, followed up until 2019. We used Cox model with time-dependent exposure and covariates to estimate the hazard ratio (HR) of death, major-adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD) in a propensity-score overlap-weighted cohort of continued versus discontinued-metformin users. Results: Of 36,940 metformin users with new-onset eGFR<30 ml/min/1.73m2, 8400 (22.7%) discontinued metformin within 6 months whereas 28,540 (77.3%) continued with metformin. The median metformin daily dose was 1000 [interquartile range, IQR: 1000, 1000] mg in continued-metformin users. During a median follow-up of 3.5 (IQR:1.8-5.8) years, 15.3%, 16.6%, and 28.1% had incident MACE, heart failure, and ESKD respectively, and 41.5% died. Compared to continued-metformin use, discontinuation was associated with higher risk of MACE (weighted and adjusted HR=1.42, 95% CI: 1.31-1.54), heart failure (HR=1.70, 1.58-1.83), ESKD (HR=1.73, 1.63-1.83), and death (HR=1.24, 1.19-1.29). Results were consistent in patients with and without established cardiovascular diseases (CVD). Conclusions: Discontinuation of metformin was associated with increased risk of cardiovascular-renal events, regardless CVD status. Continuation of metformin below eGFR 30ml/min/1.73m2 may be associated with cardio-renal and mortality benefits that needs to be weighed against the risks of lactic acidosis. Disclosure A.Yang: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. M.Shi: None. H.Wu: None. E.S.H.Lau: None. J.T.K.Cheung: None. X.Zhang: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Speaker's Bureau; Abbott, AstraZeneca, Lilly, Bayer Inc., Boehringer Ingelheim Inc. A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. Funding Chinese University of Hong Kong
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