Risk of lactic acidosis in type 2 diabetes patients using metformin: A case control study

PLoS One. 2018 May 8;13(5):e0196122. doi: 10.1371/journal.pone.0196122. eCollection 2018.

Abstract

Background: Metformin constitutes first-line treatment of type 2 diabetes mellitus. It is presumed to have lactic acidosis as a dangerous, but rare, side effect.

Objectives: To estimate the incidence rate of lactic acidosis in patients with type 2 diabetes mellitus as well as to estimate the relative risk of lactic acidosis associated with metformin treatment.

Methods: This is a population-based combined cohort and case-control study among patients with type 2 diabetes mellitus who were acutely admitted with lactic acidosis at Odense University Hospital, Denmark; in the period from 1st June 2009 to 1st October 2013. The patients included as cases were all acutely hospitalized with lactic acidosis (pH <7.35 and lactate ≥2.0 mmol/l). For each case, we identified 24 age- and sex-matched controls sampled from the same cohort with type 2 diabetes mellitus. The use of metformin identified by using a prescription database. Analyses included multivariable logistic regression and adjusting for predefined confounding: renal function, HbA1c, comorbidity and diabetes duration.

Results: Our cohort included 10,652 patients with type 2 diabetes mellitus with a median age of 74 years, and 51.5% were male. During follow-up, 163 individuals were hospitalized with lactic acidosis, corresponding to an incidence rate of 391/100,000 person years. Use of metformin was not associated with lactic acidosis: adjusted odds ratio was 0.79 (95%CI 0.54-1.17).

Conclusion: Among patients with type 2 diabetes mellitus, the incidence rate of acute hospitalization with lactic acidosis was 391/100,000 person years. Use of metformin did not increase the risk of lactic acidosis. However, comorbidity seems to be an important risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / chemically induced*
  • Acidosis, Lactic / epidemiology
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Comorbidity
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Incidence
  • Male
  • Metformin / adverse effects*
  • Risk Factors

Substances

  • Hypoglycemic Agents
  • Metformin

Grant support

Professor Henning Beck-Nielsen received reimbursement of travel expenses from Novo Nordisk in connection with an invited lecture, but received no honorarium. Novo Nordisk had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Abdellatif Aharaz has received a PhD stipendiate funded by The University of Southern Denmark and Nordic Bioscience via Danish PhD School of Endocrinology. The University of Southern Denmark and Nordic Bioscience had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.