David M Charytan1, Scott D Solomon2, Peter Ivanovich3, Giuseppe Remuzzi4, Mark E Cooper5, Janet B McGill6, Hans-Henrik Parving7, Patrick Parfrey8, Ajay K Singh1, Emmanuel A Burdmann9, Andrew S Levey10, Kai-Uwe Eckardt11, John J V McMurray12, Larry A Weinrauch2, Jiankang Liu2, Brian Claggett2, Eldrin F Lewis2, Marc A Pfeffer2. 1. Nephrology Division, Department of Medicine, NYU Langone Medical Center, New York, New York. 2. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 3. Renal Division, Northwestern University, Chicago, Illinois. 4. Division of Nephrology, L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy and Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy. 5. Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia. 6. Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri. 7. Division of Endocrinology, Metabolism and Lipid Research, Rigshospitalet Copenhagen University Hospital, Copehnahgen, Denmark. 8. Division of Nephrology, Health Sciences Centre, St. John's, Canada. 9. Division of Nephrology, University of Sao Paulo Medical School, Sao Paulo, Brazil. 10. Division of Nephrology, Tufts Medical Center, Boston, Massachusetts. 11. Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany. 12. Division of Cardiology, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Abstract
AIMS: Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. MATERIALS AND METHODS: All-cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metforminusers and non-users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin-alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non-users and in multivariable proportional hazards models. RESULTS: There were 591 individuals who used metformin at baseline and 3447 non-users. Among propensity-matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non-users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all-cause mortality (HR, 0.49; 95% CI, 0.36-0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32-0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51-0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61-0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65-1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. CONCLUSIONS:Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.
RCT Entities:
AIMS: Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. MATERIALS AND METHODS: All-cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non-users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin-alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non-users and in multivariable proportional hazards models. RESULTS: There were 591 individuals who used metformin at baseline and 3447 non-users. Among propensity-matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non-users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all-cause mortality (HR, 0.49; 95% CI, 0.36-0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32-0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51-0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61-0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65-1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. CONCLUSIONS:Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.
Authors: Godela M Brosnahan; Wei Wang; Berenice Gitomer; Taylor Struemph; Diana George; Zhiying You; Kristen L Nowak; Jelena Klawitter; Michel B Chonchol Journal: Am J Kidney Dis Date: 2021-08-12 Impact factor: 8.860