Abstract
In 1995, the oral antihyperglycemic agent, metformin, was introduced in the United
States for treating diabetes mellitus. Rare cases of metformin-associated lactic acidosis
caused by the accumulation of the drug in patients with renal dysfunction have been
described, although a detailed time course of the resulting metabolic derangements
has not been reported. A case of metformin-associated lactic acidosis is presented
along with key serial laboratory abnormalities observed during the treatment phase.
The patient made a complete recovery following therapy with hemodialysis and supportive
care.
Keywords
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References
- Focus on metformin.Formulary. 1995; 30: 383-387
Misbin RI, Green L, Stadel BV, Gueriguian JL, Gubbi A, Fleming GA. Lactic acidosis in patients with diabetes treated with metformin [letter]. N Engl J Med 1998;338:265–6.
- Farewell to phenformin for treating diabetes mellitus.Ann Intern Med. 1975; 83: 567-568
- Metformin.N Engl J Med. 1996; 334: 574-579
- Incidence of severe side effects during therapy with sulfonylureas and biguanides.Horm Metab Res. 1985; 15: 111-115
Wiholm BE, Myrhed M. Metformin-associated lactic acidosis in Sweden. 1977–1991. Eur J Clin Pharmacol 1993;44:589–91.
- Lactic acidosis rates in type 2 diabetes.Diabetes Care. 1998; 21: 1659-1663
- Metformin and lactic acidosis. Guilt by association?.Diabetes Care. 1998; 21: 1587-1588
- Determination of metformin in plasma by high-performance liquid chromatography after ultrafiltration.J Chromatography B. 1998; 716: 299-304
- The hyperlactatemic effect of biguanides.Rivista Europea Per Le Scienze Mediche e Farmacologiche. 1989; 11: 45-49
- Metabolic effects of metformin in non-insulin-dependent diabetes mellitus.N Engl J Med. 1995; 333: 550-554
- Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial.Ann Intern Med. 1999; 131: 182-188
- Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus.N Engl J Med. 1995; 333: 541-549
- Pharmacologic therapy for type 2 diabetes mellitus.Ann Intern Med. 1999; 131: 281-303
- Effects of metformin on glucose and glucagon regulated gluconeogenesis in cultured normal and diabetic hepatocytes.Biochem Pharmacol. 1994; 48: 949-954
- Effects of metformin on lactate uptake and gluconeogenesis in the perfused rat liver.Diabetes. 1997; 46: 1406-1413
- Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus.J Clin Endocrinol Metabol. 1996; 81: 4059-4067
- Cellular mechanism of action of metformin.Diabetes Care. 1990; 13: 696-704
- Effects of metformin on glucose metabolism of isolated perfused rat skeletal muscle.Arzneimittel-Forschung. 1977; 27: 1573-1576
- The effect of short-term administration of antidiabetic biguanide derivatives on the blood lactate levels in healthy subjects.Diabetologia. 1978; 14: 89-94
- Role of metformin accumulation in metformin-associated lactic acidosis.Diabetes Care. 1995; 18: 779-784
- The management of metformin overdose.Anaesthesia. 1998; 53: 698-701
- Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin.Int J Clin Pharmacol Ther Toxicol. 1989; 27: 285-288
- Metformin-associated lactic acidosis.Am J Med. 1996; 101: 109-110
Chalopin J-M, Tanter Y, Besancenot J-F, Cabanne J-F, Rifle G. Treatment of metformin-associated lactic acidosis with closed recirculation bicarbonate-buffered hemodialysis [letter]. Arch Intern Med. 1984;144:203–5.
- Cranial CT findings in metformin (Glucophage)-induced lactic acidosis.J Computer Assisted Tomography. 1998; 22: 528-529
- Severe lactic acidosis in patient receiving continuous ambulatory peritoneal dialysis.BMJ. 1993; 307: 1056-1057
- Bicarbonate haemodialysis as a treatment of metformin overdose.Nephrol Dial Transplant. 1997; 12: 1046-1047
Bristol-Myers Squibb Company. Glucophage®: metformin hydrochloride tablets [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 1999.
- Effect of metformin on glucose metabolism in the splanchnic bed.Br J Pharmacol. 1992; 105: 1009-1013
- Metabolic and drug distribution studies do not support direct inhibitory effects of metformin on intestinal glucose absorption.Diabete et Metabolisme. 1994; 20: 532-539
- Survival after metformin-associated lactic acidosis in peritoneal dialysis-dependent renal failure.Am J Med. 1997; 102: 486-488
- Metformin-induced lactic acidosis associated with acute renal failure.Am J Nephrol. 1996; 16: 520-522
- Metformin-associated lactic acidosis in diabetic patients with acute renal failure. A critical analysis of its pathogenesis and prognosis.Nephrol Dial Transplant. 1994; 9: 126-129
- Biguanide-associated lactic acidosis. Case report and review of the literature.Arch Intern Med. 1992; 152: 2333-2336
- Metformin-induced lactic acidosis.Res Comm Chem Pathol Pharmacol. 1981; 33: 21-31
- The effects of metformin compared to the effects of phenformin on the lactate production and the metabolism of isolated parenchymal rat liver cell.Acta Pharmacologica et Toxicologica. 1984; 54: 327-332
- Ketosis.Kidney Int. 1981; 20: 416-425
- Alcoholic ketoacidosis—a review.J Emerg Med. 1987; 5: 399-406
- Lactic acidosis due to metformin therapy in a low risk patient.Postgrad Med J. 1988; 64: 230-231
- Lactic acidosis with therapeutic metformin blood level in a low-risk diabetic patient.Diabetes Care. 1998; 21: 1364-1365
Lalau JD, Race J-M, Brinquin L. Lactic acidosis in metformin therapy. Relationship between plasma metformin concentration and renal function [letter]. Diabetes Care 1998;21:1366–7.
- Bicarbonate haemodialysis.Intensive Care Med. 1987; 13: 383-387
- The cellular basis of conventional and experimental pharmacotherapies for circulatory shock.Anaesth Pharmacol Rev. 1994; 2: 115-127
- Lactic acidosis.in: Carlson R.W Geheb M.A Principles & practice of medical intensive care. W. B. Saunders, Philadelphia1993: 1231-1245
- Contraindications to metformin therapy in patients with NIDDM.Diabetes Care. 1997; 20: 925-928
- Calculation of plasma bicarbonate concentration versus measurement of serum CO2 content. pK’ revisited.Clin Intensive Care. 1995; 6: 15-20
Article info
Publication history
Accepted:
October 17,
2000
Received in revised form:
September 22,
2000
Received:
May 17,
2000
Identification
Copyright
© 2001 Elsevier Science Inc. Published by Elsevier Inc. All rights reserved.
