Lactic acidosis associated with metformin in diabetic patients with chronic kidney disease: a multicentre case-control study using electronic health records

Abstract

Background: Several studies have assessed the risk of lactic acidosis with metformin use. However, data of this association in patients with renal impairment are still scarce and controversial. Our aim was therefore to assess the association between metformin and lactic acidosis in Spanish type 2 diabetic patients with chronic kidney disease.Methods: A case-control study (ALIMAR-C2) was performed using the electronic health records from hospitals linked to their corresponding primary healthcare regions. The cases were adult (≥18 years) diabetic patients with chronic kidney disease, admitted to seven Spanish hospitals from 2010 to 2016. Ten controls (≥18 years, diabetic patients with chronic kidney disease) per case were selected from the population within the same primary healthcare region of the hospital cases. The patients’ hospital health records were linked to their corresponding primary healthcare information. Analyses included multivariable logistic regression and adjustment for potential confounders. Results: Our study included 126 cases and 1,260 matched controls. The current use of metformin and administration at high doses (>2g) were associated with lactic acidosis (adjusted OR: 1.92, 95% CI: 1.21-3.03; OR: 3.13, 95% CI: 1.63-6.01, respectively). The estimated case fatality rate was 46.8% (95% CI: 38.3-55.5%). An increased risk of lactic acidosis was observed In patients with mild to moderate renal impairment (OR: 3.41, 95% CI: 1.48-7.85). As an unexpected finding, diuretic drugs use was also associated with lactic acidosis (OR: 2.73, 95% CI: 1.67 - 4.46).Conclusions: Metformin was associated with an increased risk of lactic acidosis in patients with type 2 diabetes mellitus and chronic kidney disease. New data is needed to confirm the association between diuretic drugs and lactic acidosis in this group of patients.