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

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

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.

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.

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).

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.