Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study

Carlos A. Alvarez, Ethan A. Halm, Mary Jo V. Pugh, Darren K. McGuire, Sean Hennessy, Richard T. Miller, Ildiko Lingvay, Scott M. Vouri, Andrew R. Zullo, Hui Yang, Matt Chansard, Eric M. Mortensen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalEndocrinology, Diabetes and Metabolism
DOIs
StateAccepted/In press - 2020
Externally publishedYes

Keywords

  • chronic kidney disease
  • diabetes mellitus
  • lactic acidosis
  • metformin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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