Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

AIM: To provide evidence on the cardiovascular and renal safety of metformin in chronic kidney disease (CKD) stages 3 to 4. MATERIALS AND METHODS: This post hoc analysis compared participants with an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73m2 in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) and the Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (SAVOR-TIMI 53) trials taking metformin, with those not exposed to metformin during these trials, using a propensity-matching approach. Adjusted Cox proportional hazards models were used to assess risk of major adverse cardiovascular events (MACE) and all-cause mortality (ACM). Metformin effect on eGFR slope was calculated using a mixed-model repeated measures analysis, and the number of lactic acidosis events was tabulated. RESULTS: No strong trend for lower metformin doses with lower eGFR values was observed in either the EXSCEL or SAVOR-TIMI 53 trials. In the 1745 metformin-using participants matched to non-metformin users, metformin had neutral effects on MACE (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.76-1.08; P = 0.28) and ACM (HR 0.86, 95% CI 0.70-1.07; P = 0.18), with no interaction by CKD stage, or with use of exenatide or saxagliptin. An improvement in eGFR slope was observed with metformin in the CKD stage 3B cohort in SAVOR-TIMI 53, but not in other groups. CONCLUSIONS: This analysis of participants with CKD stages 3 to 4 from two cardiovascular outcomes trials supports the cardiorenal safety of metformin, but does not suggest a consistent benefit on MACE, ACM, or eGFR slope across this population.

Original publication




Journal article


Diabetes Obes Metab

Publication Date





1101 - 1110


cardiovascular disease, metformin, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Humans, Kidney, Metformin, Renal Insufficiency, Chronic