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Letters: Observations

Is Metformin Safe in Patients With Mild Renal Insufficiency?

  1. Amir Kazory, MD1,
  2. Katherine Walsh, MD2,
  3. Eloise Harman, MD3 and
  4. Zvi Talor, MD1
  1. 1Division of Nephrology, University of Florida College of Medicine at UF Shands Hospital, Gainesville, Florida
  2. 2Department of Internal Medicine, University of Florida College of Medicine at UF Shands Hospital, Gainesville, Florida
  3. 3Division of Pulmonary Medicine, University of Florida College of Medicine at UF Shands Hospital, Gainesville, Florida
  1. Address correspondence to Katherine Walsh, MD, Department of Internal Medicine, Shands Hospital, University of Florida, 1600 SW Archer Rd., Gainesville, FL 32610. E-mail: walshkj{at}medicine.ufl.edu
Diabetes Care 2007 Feb; 30(2): 444-444. https://doi.org/10.2337/dc06-2155
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Among the first million patients who received metformin in the U.S., 47 patients developed metformin-associated lactic acidosis (MALA), with 43 having predisposing factors for lactic acidosis (including moderate to severe renal failure and congestive heart failure) (1). Although there was initial concern, studies have suggested that MALA is secondary to underlying conditions and represents a coincidental finding (2,3). While the current consensus is that the risk of lactic acidosis is negligible when metformin is used as labeled (4), we present a patient who developed MALA in the absence of currently recognized contraindications to metformin.

A 55-year-old man with hypertension, type 2 diabetes, and mild renal insufficiency (measured creatinine clearance 91 ml/min) presented with sudden onset of fatigue, vomiting, and altered mental status after performing strenuous yard work without sufficient hydration. His medications included nifedipine, captopril, hydrochlorothiazide, glyburide, and metformin.

The patient rapidly developed respiratory distress and hypotension necessitating intubation and vasoactive agents. Laboratory studies revealed a serum creatinine level of 9.4 mg/dl, pH 6.98, CO2 <6 mmol/l, and lactic acid 27 mmol/l. Evaluation using a computed tomography scan and magnetic resonance angiography of the abdomen/pelvis, various cultures and cardiac echocardiogram could not reveal an etiology for lactic acidosis. Serum metformin level (ARUP Laboratories, Salt Lake City, UT) was 8 mg/l (therapeutic range 1–2). Continuous venovenous hemofiltration was initiated immediately. Conservative management was followed by rapid amelioration of his general status. He was extubated within 24 h, continuous venovenous hemofiltration was stopped after 36 h, and he was discharged 6 days after presentation without deficits.

This case is unique in that MALA developed in the absence of currently recognized risk factors or predisposing conditions. Although this patient had mild impairment of kidney function, contraindication criteria for the use of metformin were not met (5). The patient was taking 2 g metformin per day, which is within the recommended therapeutic range.

In our opinion, a threshold serum creatinine level above normal range should not be considered safe for metformin use because renal function can rapidly deteriorate in patients with even mild underlying kidney disease, resulting in accumulation of metformin and development of MALA. We suggest that consideration be given to avoiding metformin in patients with any degree of renal dysfunction.

Footnotes

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References

  1. ↵
    Misbin RI, Green L, Stadel BV, Gueriquian JL, Gubbi A, Fleming GA: Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338: 265–266, 1998
    OpenUrlCrossRefPubMedWeb of Science
  2. ↵
    Misbin RI: The phantom of lactic acidosis due to metformin in patients with diabetes. Diabetes Care 27: 1791–1793, 2004
    OpenUrlFREE Full Text
  3. ↵
    Salpeter S, Greyber G, Pasternak G, Salpeter E: Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Sys Rev no. CD002967, 2006
  4. ↵
    Luft FC: Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 12: S15–S19, 2001
    OpenUrlAbstract/FREE Full Text
  5. ↵
    Holstein A, Stumvoll M: Contraindications can damage your health: is metformin a case in point? Diabetologia 48: 2454–2459, 2005
    OpenUrlCrossRefPubMedWeb of Science
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Diabetes Care: 30 (2)

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February 2007, 30(2)
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Is Metformin Safe in Patients With Mild Renal Insufficiency?
Amir Kazory, Katherine Walsh, Eloise Harman, Zvi Talor
Diabetes Care Feb 2007, 30 (2) 444; DOI: 10.2337/dc06-2155

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Is Metformin Safe in Patients With Mild Renal Insufficiency?
Amir Kazory, Katherine Walsh, Eloise Harman, Zvi Talor
Diabetes Care Feb 2007, 30 (2) 444; DOI: 10.2337/dc06-2155
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