Development, implementation and outcome analysis of semi-automated alerts for metformin dose adjustment in hospitalized patients with renal impairment

Pharmacoepidemiol Drug Saf. 2016 Oct;25(10):1204-1209. doi: 10.1002/pds.4062. Epub 2016 Jul 14.


Purpose: Overdosing of the oral antidiabetic metformin in impaired renal function is an important contributory cause to life-threatening lactic acidosis. The presented project aimed to quantify and prevent this avoidable medication error in clinical practice.

Methods: We developed and implemented an algorithm into a hospital's clinical information system that prospectively identifies metformin prescriptions if the estimated glomerular filtration rate is below 60 mL/min. Resulting real-time electronic alerts are sent to clinical pharmacologists and pharmacists, who validate cases in electronic medical records and contact prescribing physicians with recommendations if necessary.

Results: The screening algorithm has been used in routine clinical practice for 3 years and generated 2145 automated alerts (about 2 per day). Validated expert recommendations regarding metformin therapy, i.e., dose reduction or stop, were issued for 381 patients (about 3 per week). Follow-up was available for 257 cases, and prescribers' compliance with recommendations was 79%. Furthermore, during 3 years, we identified eight local cases of lactic acidosis associated with metformin therapy in renal impairment that could not be prevented, e.g., because metformin overdosing had occurred before hospitalization.

Conclusions: Automated sensitive screening followed by specific expert evaluation and personal recommendations can prevent metformin overdosing in renal impairment with high efficiency and efficacy. Repeated cases of metformin-associated lactic acidosis in renal impairment underline the clinical relevance of this medication error. Our locally developed and customized alert system is a successful proof of concept for a proactive clinical drug safety program that is now expanded to other clinically and economically relevant medication errors. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: clinical decision support; drug safety; interventional pharmacoepidemiology; metformin; pharmacoepidemiology; renal impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / chemically induced
  • Acidosis, Lactic / prevention & control
  • Aged
  • Algorithms
  • Automation
  • Dose-Response Relationship, Drug
  • Drug Overdose / prevention & control
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Hospital Information Systems
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Male
  • Medical Order Entry Systems*
  • Medication Errors / prevention & control
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Pharmacists / organization & administration
  • Professional Role
  • Renal Insufficiency / physiopathology*


  • Hypoglycemic Agents
  • Metformin