TY - JOUR
T1 - Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease
AU - Charytan, David M.
AU - Solomon, Scott D.
AU - Ivanovich, Peter
AU - Remuzzi, Giuseppe
AU - Cooper, Mark E.
AU - McGill, Janet B.
AU - Parving, Hans Henrik
AU - Parfrey, Patrick
AU - Singh, Ajay K.
AU - Burdmann, Emmanuel A.
AU - Levey, Andrew S.
AU - Eckardt, Kai Uwe
AU - McMurray, John J.V.
AU - Weinrauch, Larry A.
AU - Liu, Jiankang
AU - Claggett, Brian
AU - Lewis, Eldrin F.
AU - Pfeffer, Marc A.
N1 - Funding Information:
M. P. has received research grant support from Amgen, Celladon, Novartis and Sanofi (significant); has received consultantcy fees from Bayer, Genzyme, GlaxoSmithKline, Janssen, Lilly, Medicines Company, Merck, Novartis, Novo Nordisk, Relypsa, Salix, Sanofi, Thrasos and Vericel (modest) and from Boehringer Ingelheim, DalCor and Teva (significant); and holds stock options in DalCor.
Funding Information:
D. C. has received a research grant from Janssen Pharmaceuticals (significant) and funds for service from DSMB-Astra Zeneca. S. S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, BMS, Celladon, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur and Theracos; and has received consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Corvia, Gilead, GSK, Ironwood, Merck, Novartis, Pfizer, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, Abiomed and Janssen. A. K. S. has received a research grant from Glaxo Smith Kline (significant). A. L. has received a research grant from Amgen as a member of the TREAT Steering Committee. E. B. has received fees for consultancy and Advisory Board membership from Fresenius (modest). J. M. has received grants from Dexcom, Novartis, AZ/BMS, Medtronic (significant); has received fees for Advisor/Consultant from Bayer, BI/Lilly, NovoNordisk (modest); has received fees for Speakers' Bureau from Janssen (significant), Dexcom (modest), Mannkind (modest) and Aegerion (modest). E. L. has received a research grant from Sanofi (significant).
Funding Information:
D. C. has received a research grant from Janssen Pharmaceuticals (significant) and funds for service from DSMB-Astra Zeneca. S. S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, BMS, Celladon, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur and Theracos; and has received consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Corvia, Gilead, GSK, Ironwood, Merck, Novartis, Pfizer, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, Abiomed and Janssen. A. K. S. has received a research grant from Glaxo Smith Kline (significant). A. L. has received a research grant from Amgen as a member of the TREAT Steering Committee. E. B. has received fees for consultancy and Advisory Board membership from Fresenius (modest).
Funding Information:
J. M. has received grants from Dexcom, Novartis, AZ/BMS, Medtronic (significant); has received fees for Advisor/Consultant from Bayer, BI/Lilly, NovoNordisk (modest); has received fees for Speakers' Bureau from Janssen (significant), Dexcom (modest), Mannkind (modest) and Aegerion (modest). E. L. has received a research grant from Sanofi (significant). K-U. E. has received grant support from Amgen, Astra Zeneka, Vifor and FMC; and has received consultancy fees from Akebia and lecture fees from Bayer and Aventis. P. I. has received fees for membership on Data Safety Monitoring Committees of Amgen (modest), Applied Clinical Intelligence, LLC (modest) and Astra Zeneca; and for membership on the Medical Advisory Board of Physician Software Systems, LLC (equity, modest, <5%). G. R. has consultancy agreements Alnylam and F. Hoffmann–La Roche SA., with no personal remuneration accepted (compensations are paid to his institution for research and educational activities) and also with Boehringer Ingelheim, Handok Inc. and Janssen Research and Development. B. C. has nothing to disclose. J. L. has nothing to disclose. L. A. W. has received reimbursement for travel expenses from Amgen and fees related to service on clinical event committees from Amgen, Sanofi and Novartis; and has received fees for serving as site principal investigator for Roche, Wyeth and Boehringer Ingelheim pharmaceutical trials. P. P. has received speaker fees from Amgen (modest). H.-H. P. has received consulting fees from Abbvie (significant). M. C. has received grants from NovoNordisk (significant); has received consultantcy fees from MSD, Servier, Eli-Lilly, Novo-Nordisk, Bayer (modest) and from Boehringer Ingelheim and AstraZeneca (significant). J. M. has nothing to disclose.
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - cardiovascular disease
KW - diabetes complications
KW - diabetic nephropathy
KW - metformin
UR - http://www.scopus.com/inward/record.url?scp=85062630901&partnerID=8YFLogxK
U2 - 10.1111/dom.13642
DO - 10.1111/dom.13642
M3 - Article
C2 - 30672083
AN - SCOPUS:85062630901
VL - 21
SP - 1199
EP - 1208
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 5
ER -