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All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003\u201013 were included. The outcome was LA hospitalization or serum lactate\u00a0&gt;5\u00a0mEq\/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 320\u00a0882 patients were included, contributing a total of 1\u00a0331\u00a0784 person\u2010years of follow\u2010up. LA occurred in 2\u00a0665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93\u20102.08) per 1000 person\u2010years. Metformin exposure in the prior 3\u00a0months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69\u20102.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71\u20101.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19\u20104.35 in CKD 3a, HR 3.34, 95% CI 1.95\u20105.72 in CKD 3b, HR 7.87, 95% CI 3.51\u201017.61 in CKD stage 4&amp;5.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Metformin was not associated with an elevated risk of LA in persons with stage 1\u20102 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.170","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T13:18:07Z","timestamp":1594991887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested 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