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Background: Diabetes often causes kidney disease. In this study, we sought to evaluate if metformin use was associated with death or kidney events in patients with diabetes and concurrent reduced kidney function., Methods: We used data from the Veterans Health Administration, Medicare and National Death Index databases to assemble a national retrospective cohort of veterans who were using metformin or sulfonylureas from 2001 through 2016 and who began follow-up at an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m 2 . The primary composite outcome was a kidney event (i.e., 40% decline in eGFR or end-stage renal disease) or death. The secondary outcome was a kidney event (eGFR decline or end-stage renal disease). We weighted the cohort using propensity scores and used Cox proportional models to estimate the cause-specific hazard of outcomes and of treatment nonpersistence as a competing risk. We stratified follow-up into 2 periods, namely the first 360 days from the start of follow-up, and 361 days and beyond., Results: In the first 360 days, the propensity score-weighted cohort included 24 883 patients who used metformin and 24 998 who used sulfonylureas. There were 33.5 (95% confidence interval [CI] 30.9-36.3) and 43.0 (95% CI 40.1-46.0) deaths or kidney events per 1000 person-years for patients who used metformin or sulfonylureas, respectively (hazard ratio [HR] 0.78, 95% CI 0.71-0.85). For the secondary outcome of kidney events, the HR was 0.94 (95% CI 0.67-1.33). In the second period from 361 days onward, the primary outcome event rate was 26.5 (95% CI 24.7-28.5) per 1000 person-years for those who used metformin, compared with 36.3 (95% CI 34.2-38.6) per 1000 person-years for those who used sulfonylureas (HR 0.73, 95% CI 0.67-0.79). Results were consistent for kidney events alone (HR 0.73, 95% CI 0.59-0.91)., Interpretation: Metformin use for 361 days or longer after reaching an eGFR of less than 60 mL/min/1.73 m 2 was associated with decreased likelihood of kidney events or death in patients with diabetes, compared with use of sulfonylureas. Metformin provided end-organ protection, in addition to glucose control., Competing Interests: Competing interests: Outside the submitted work, Adriana Hung reports funding from Veterans Affairs and the Vertex trial; consulting fees from the National Heart, Lung, and Blood Institute; and speaking fees from Stanford Medical Grand Rounds. Amber Hackstadt reports participation with the data safety and monitoring board for the PILOT trial, and with the independent monitoring committee for a study on telehealth and pain. Carlos Grijalva reports funding from Campbell Alliance, Syneos Health, Sanofi, the United States Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, the National Institutes of Health and the US Food and Drug Administration. He also reports consulting fees from Merck, Pfizer and Sanofi-Pasteur. Christianne Roumie reports funding from the Center for Diabetes Translation Research. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)