Metformin-Induced Lactic Acidosis Is Found to Be Rare


Am Fam Physician. 2004 Apr 15;69(8):1991.

Clinical Question: What is the risk of lactic acidosis accompanying metformin therapy in patients with type 2 diabetes?

Setting: Outpatient (any)

Study Design: Systematic review

Synopsis: The authors of this study combined the results of all randomized controlled trials and observational studies to determine the risk of lactic acidosis with metformin. The literature search was thorough and included unpublished data. Two independent reviewers evaluated the articles for inclusion. The methodologic quality of the studies was evaluated using modified quality criteria. Of the 194 studies in the analysis, 126 were randomized controlled studies, and 68 were observational research. More than 18,000 participants in these studies received metformin for an average of 2.1 years (36,893 patient-years).

No cases of lactic acidosis were seen in the metformin-treated group or in the comparison group. Undoubtedly, patients with risk factors for lactic acidosis were not enrolled in any of the studies, and monitoring was more intense than in typical practice. Population studies estimate the incidence of lactic acidosis to be between two and nine cases per 100,000 patient-years, which also is the incidence of lactic acidosis in patients with diabetes who are not receiving metformin. Using these numbers, one to three cases of lactic acidosis would have been expected in the current study. Several studies evaluated lactic acid levels in metformin-treated patients and found no difference in baseline lactic acid levels compared with patients not treated with metformin.

Bottom Line: The link between metformin and lactic acidosis, when this agent is used as prescribed, is tenuous. The bigger question is whether the risk of lactic acidosis truly increases when we relax criteria and prescribe metformin to patients who were previously forbidden to take it. (Level of Evidence: 1a)


Salpeter SR, et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med. November 24, 2003;163:2594–602.

Used with permission from Shaughnessy AF. Metformin-induced lactic acidosis extremely rare. Accessed online January 26, 2004, at: http://www.InfoPOEMs.com.



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