Open AccessLactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case‐control study
Author(s) -
Alvarez Carlos A.,
Halm Ethan A.,
Pugh Mary Jo V.,
McGuire Darren K.,
Hennessy Sean,
Miller Richard T.,
Lingvay Ildiko,
Vouri Scott M.,
Zullo Andrew R.,
Yang Hui,
Chansard Matt,
Mortensen Eric M.
Publication year - 2021
Publication title -
endocrinology, diabetes and metabolism
Language(s) - English
Resource type - Journals
ISSN - 2398-9238
DOI - 10.1002/edm2.170
Subject(s) - medicine , metformin , kidney disease , diabetes mellitus , hazard ratio , type 2 diabetes , incidence (geometry) , lactic acidosis , retrospective cohort study , nested case control study , case control study , endocrinology , confidence interval , insulin , physics , optics
Objective Compare rates of lactic acidosis (LA) among metformin‐exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD). Research Design and Methods Retrospective, nested case‐control study using data from national VA Corporate Data Warehouse. All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003‐13 were included. The outcome was LA hospitalization or serum lactate >5 mEq/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications. Results Overall, 320 882 patients were included, contributing a total of 1 331 784 person‐years of follow‐up. LA occurred in 2 665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93‐2.08) per 1000 person‐years. Metformin exposure in the prior 3 months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69‐2.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71‐1.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19‐4.35 in CKD 3a, HR 3.34, 95% CI 1.95‐5.72 in CKD 3b, HR 7.87, 95% CI 3.51‐17.61 in CKD stage 4&5. Conclusion Metformin was not associated with an elevated risk of LA in persons with stage 1‐2 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.