Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world

Pharmacoepidemiol Drug Saf. 2013 Oct;22(10):1027-35. doi: 10.1002/pds.3501. Epub 2013 Aug 19.


Objective: We compared and contrasted guidelines on metformin treatment in patients with chronic kidney disease (CKD) around the world, with the aim of helping physicians to refine their analysis of the available evidence before deciding whether to continue or withdraw this drug.

Methods: We performed a systematic research for metformin contraindications in: (i) official documents from the world's 20 most populated countries and the 20 most scientifically productive countries in the field of diabetology and (ii) publications referenced in electronic databases from 1990 onwards.

Results: We identified three international guidelines, 31 national guidelines, and 20 proposals in the scientific literature. The criteria for metformin withdrawal were (i) mainly qualitative in the most populated countries; (ii) mainly quantitative in the most scientifically productive countries (with, in all cases, a suggested threshold for withdrawing metformin); and (iii) quantitative in all, but one of the literature proposals, with a threshold for withdrawal in most cases (n = 17) and/or adjustment of the metformin dose as a function of renal status (n = 8). There was a good degree of consensus on serum creatinine thresholds; whereas guidelines based on estimated glomerular filtration rate thresholds varied from 60 mL/minute/1.73 m(2) up to stage 5 CKD. Only one of the proposals has been tested in a prospective study.

Conclusions: In general, proposals for continuing or stopping metformin therapy in CKD involve a threshold (whether based on serum creatinine or estimated glomerular filtration rate) rather than the dose adjustment as a function of renal status (in stable patients) performed for other drugs excreted by the kidney.

Keywords: Type 2 diabetes; drug accumulation; kidney disease; lactic acidosis; metformin; pharmacoepidemiology.

Publication types

  • Review

MeSH terms

  • Contraindications
  • Diabetes Complications / complications*
  • Diabetes Complications / urine
  • Diabetes Mellitus / drug therapy*
  • Global Health
  • Guidelines as Topic*
  • Humans
  • Metformin / administration & dosage*
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / urine
  • Withholding Treatment*


  • Metformin