MAL-Adaptive Do We Avoid Metformin Unnecessarily? Chris Terpening, PhD, PharmD, BCACPDisclosures J Am Board Fam Med. 2014;27(1):136-141.


Convention holds that the use of metformin is contraindicated in many patients secondary to concerns about lactic acidosis. However, current evidence suggests that metformin-associated lactic acidosis is at most idiosyncratic. Awareness of the current evidence should permit broader use of this valuable medication.

Conclusions and Recommendations

While there are cases of metformin overdose resulting in lactic acidosis in the absence of confounders, even these situations seem to be idiosyncratic. Current contraindications do not seem to alter the incidence of lactic acidosis and simply serve to deny many patients the clear benefits of metformin. While the data may support an "all metformin, all the time" approach, simple pragmatism suggests a more cautious approach. Instructing patients to interrupt metformin therapy whenever they have a significant acute illness is rational and encouraged. If the illness is severe enough to require hospitalization, insulin can be substituted in a closely monitored fashion. It is, however, imperative to make sure that a temporary illness does not become a permanent bar to metformin use.

The practitioner should make sure to restart metformin at the earliest opportunity, no later than discharge from the hospital. In terms of the most common contraindication, chronic renal impairment, any GFR cutoff seems arbitrary because the risk has not been clearly defined. However, there seems to be evidence of safety with GFRs as low as 30 mL/min. Several nations (eg, the United Kingdom, Australia, the Netherlands) already have adopted that as a recommendation. The joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes states that "use down to a GFR of 30 mL/min, with dose reduction advised at 45 mL/min … appear[s] very reasonable."

Given this wide level of support, one may hope that the FDA will alter the contraindications in the package insert accordingly. Until such time, the current listed contraindications should not be regarded as absolute, but instead the practitioner should take the entire risk/benefit picture into account.


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