Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Charytan, D. M. et al. (2019) Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. Diabetes, Obesity and Metabolism, 21(5), pp. 1199-1208. (doi: 10.1111/dom.13642) (PMID:30672083)

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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 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.

Item Type:Articles
Additional Information:Funding information: The TREAT trial was funded by Amgen.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Charytan, D. M., Solomon, S. D., Ivanovich, P., Remuzzi, G., Cooper, M. E., McGill, J. B., Parving, H.-H., Parfrey, P., Singh, A. K., Burdmann, E. A., Levey, A. S., Eckardt, K.-U., McMurray, J. J.V., Weinrauch, L. A., Liu, J., Claggett, B., Lewis, E. F., and Pfeffer, M. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetes, Obesity and Metabolism
Publisher:Wiley
ISSN:1462-8902
ISSN (Online):1463-1326
Published Online:22 January 2019

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