Main Article Content
Abstract
Metformin-Associated Lactic Acidosis (MALA), a potential complication of metformin therapy in type 2 diabetes patients. It highlights the medication's role in managing blood glucose, its influence on renal function, and the associated risk factors, including age and comorbidities. The pathophysiology of MALA is explored, emphasizing how metformin affects mitochondrial function and leads to lactate accumulation and acidosis. A clinical case presentation underscores the real-world implications of this condition. The article concludes by stressing the importance of early recognition and discontinuation of metformin, ultimately encouraging healthcare providers to consider individualized patient risk factors when prescribing metformin.
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References
- 1. Scheen AJ, Paquot N. Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes. Diabetes Metab. 2013 May;39(3):179-90.
- 2. Bailey CJ. Metformin: historical overview. Diabetologia. 2017 Sep;60(9):1566-1576.
- 3. Vecchio S, Giampreti A, Petrolini VM, Lonati D, Protti A, Papa P, Rognoni C, Valli A, Rocchi L, Rolandi L, Manzo L, Locatelli CA. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol (Phila). 2014 Feb;52(2):129-35.
- 4. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9
- 5. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011 Feb;50(2):81-98.
- 6. Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000 Jun 15;348 Pt 3(Pt 3):607-14.
- 7. Seidowsky A, Nseir S, Houdret N, Fourrier F. Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med. 2009 Jul;37(7):2191-6.
- 8. Lalau JD, Kajbaf F, Protti A, Christensen MM, De Broe ME, Wiernsperger N. Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm. Diabetes Obes Metab. 2017 Nov;19(11):1502-1512.
- 9. Wills BK, Bryant SM, Buckley P, Seo B. Can acute overdose of metformin lead to lactic acidosis? Am J Emerg Med. 2010 Oct;28(8):857-61.
- 10. Al-Abri SA, Hayashi S, Thoren KL, Olson KR. Metformin overdose-induced hypoglycemia in the absence of other antidiabetic drugs. Clin Toxicol (Phila). 2013 Jun;51(5):444-7.
- 11. Kimmoun A, Novy E, Auchet T, Ducrocq N, Levy B. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside. Crit Care. 2015 Apr 09;19(1):175.
- 12. Theobald J, Schneider J, Cheema N, DesLauriers C. Time to development of metformin-associated lactic acidosis. Clin Toxicol (Phila). 2020 Jul;58(7):758-762.
- 13. Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med. 1992 Nov;152(11):2333-6.
- 14. Ives Tallman C, Zhang Y, Black N, Lynch K, Fayed M, Armenian P. Refractory vasodilatory shock secondary to metformin overdose supported with VA ECMO. Toxicol Rep. 2022;9:64-67.
- 15. Wiholm BE, Myrhed M. Metformin-associated lactic acidosis in Sweden 1977-1991. Eur J Clin Pharmacol 1993;44:589-91.
References
1. Scheen AJ, Paquot N. Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes. Diabetes Metab. 2013 May;39(3):179-90.
2. Bailey CJ. Metformin: historical overview. Diabetologia. 2017 Sep;60(9):1566-1576.
3. Vecchio S, Giampreti A, Petrolini VM, Lonati D, Protti A, Papa P, Rognoni C, Valli A, Rocchi L, Rolandi L, Manzo L, Locatelli CA. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol (Phila). 2014 Feb;52(2):129-35.
4. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9
5. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011 Feb;50(2):81-98.
6. Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000 Jun 15;348 Pt 3(Pt 3):607-14.
7. Seidowsky A, Nseir S, Houdret N, Fourrier F. Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med. 2009 Jul;37(7):2191-6.
8. Lalau JD, Kajbaf F, Protti A, Christensen MM, De Broe ME, Wiernsperger N. Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm. Diabetes Obes Metab. 2017 Nov;19(11):1502-1512.
9. Wills BK, Bryant SM, Buckley P, Seo B. Can acute overdose of metformin lead to lactic acidosis? Am J Emerg Med. 2010 Oct;28(8):857-61.
10. Al-Abri SA, Hayashi S, Thoren KL, Olson KR. Metformin overdose-induced hypoglycemia in the absence of other antidiabetic drugs. Clin Toxicol (Phila). 2013 Jun;51(5):444-7.
11. Kimmoun A, Novy E, Auchet T, Ducrocq N, Levy B. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside. Crit Care. 2015 Apr 09;19(1):175.
12. Theobald J, Schneider J, Cheema N, DesLauriers C. Time to development of metformin-associated lactic acidosis. Clin Toxicol (Phila). 2020 Jul;58(7):758-762.
13. Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med. 1992 Nov;152(11):2333-6.
14. Ives Tallman C, Zhang Y, Black N, Lynch K, Fayed M, Armenian P. Refractory vasodilatory shock secondary to metformin overdose supported with VA ECMO. Toxicol Rep. 2022;9:64-67.
15. Wiholm BE, Myrhed M. Metformin-associated lactic acidosis in Sweden 1977-1991. Eur J Clin Pharmacol 1993;44:589-91.