Pedrós C, et al. - Researchers here describe study protocol for a case-control investigation (ALIMAR-C2 study) into the link between metformin and lactic acidosis in patients with type 2 diabetes mellitus and moderate-severe chronic kidney disease. From eight Spanish hospitals, computerized registered electronic health records linked to their corresponding primary care health areas from 2010 to 2016, including nearly 22.1 million person-years of follow-up, will be utilized. In order to evaluate the crude and adjusted risk of lactic acidosis related to metformin use overall and stratified by use and dose categories, and chronic kidney disease stage, logistic regression will be used. The experts will calculate the overall case fatality rate of lactic acidosis, and the case fatality rate stratified by chronic kidney disease stage. It is expected that useful information will be generated, in the ALIMAR-C2 study, regarding the risk of lactic acidosis in relation to metformin use in type 2 diabetes mellitus patients with renal impairment.