Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK

Diabet Med. 2017 Apr;34(4):485-489. doi: 10.1111/dme.13203. Epub 2016 Sep 19.


Aims: To assess risk of lactic acidosis among metformin users compared with other glucose-lowering agent users, according to renal function.

Methods: Using routine registries and databases, we conducted a cohort study. Of 43 580 metformin and 37 788 other glucose-lowering agent users in northern Denmark and 102 688 metformin and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we identified lactic acidosis using diagnostic codes. We calculated the incidence rates of lactic acidosis in metformin and other glucose-lowering agent users overall and according to baseline estimated GFR (eGFR) levels.

Results: In Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and 1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other glucose-lowering agent use, respectively. In the UK, the corresponding lactic acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per 100 000 person-years of metformin use and of other glucose-lowering agent use. The incidence rates increased with decreasing baseline eGFR in both countries. Of the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the UK experienced a decline in renal function in the year before the diagnosis.

Conclusions: Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / epidemiology*
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Databases, Factual
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Renal Insufficiency / epidemiology*
  • Renal Insufficiency / metabolism
  • Risk Factors
  • United Kingdom / epidemiology


  • Hypoglycemic Agents
  • Metformin