Risk of Metformin-Associated Lactic Acidosis (MALA) in Patients After Gastric Bypass Surgery
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Pharmacokinetic data suggest that the risk of metformin-associated lactic acidosis (MALA) may be increased after Roux-en-Y gastric bypass (RYGB) surgery. The aim of this study was to examine the impact of metformin on plasma lactate levels before and after RYGB surgery.
Retrospective study of plasma lactate levels before and 3 months after RYGB surgery in patients with type 2 diabetes mellitus (T2DM) not using metformin (MET-0, N = 58), on a stable dose (MET-S, N = 138), or on a decreasing dose (MET-D, N = 85) of metformin.
Preoperatively, lactate levels were similar in patients on metformin (1.8 ± 0.05 mmol/L) and those not on metformin (1.7 ± 0.08 mmol/L), P = 0.21. Three months postoperatively, lactate levels had decreased in all groups (P < 0.001) to 1.3 ± 0.07 (SE), 1.4 ± 0.05, and 1.2 ± 0.05 mmol/l in MET-0, MET-S, and MET-D, respectively. Lactate levels differed between the groups (P = 0.03), with the lowest level in MET-D. The number of patients with hyperlactatemia (lactate > 2 mmol/l) decreased from 31 to 14%, from 22 to 8.6%, and from 26 to 4.7% in MET-S, MET-0, and MET-D, respectively.
Mild hyperlactatemia (lactate > 2 mmol/l) is common in morbidly obese patients with T2DM. It is probably related to increase lactate production by adipocytes. Lactate levels decreased after RYGB-induced weight loss, irrespective of the use of metformin. We therefore conclude that there is no need for routinely lowering of the metformin dose after uncomplicated RYGB surgery, as long as normal renal function is preserved.
KeywordsGastric bypass (RYGB) Obesity Metformin-associated lactic acidosis (MALA)
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed Consent Statement
Does not apply.
- 1.Chamberlain JJ, Rhinehart AS, Shaefer CF, Jr., et al. Diagnosis and management of diabetes: synopsis of the 2016 American Diabetes Association standards of medical care in diabetes. Ann Intern Med 2016 Apr 19;164(8):542–552. PubMedGoogle Scholar
- 2.Salpeter SR, Greyber E, Pasternak GA,et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. The Cochrane database of systematic reviews 2010 (1):CD002967. PubMedGoogle Scholar
- 3.Gunnerson KJ. Lactic acidosis. Medscape: Medscape; 2016 [cited 2016 16-9-2016]. Available from: http://emedicine.medscape.com/article/167027-overview
- 4.Eppenga WL, Lalmohamed A, Geerts AF, et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care 2014 Aug;37(8):2218–2224. PubMedGoogle Scholar
- 5.van Berlo-van de Laar IR, Vermeij CG, Doorenbos CJ. Metformin associated lactic acidosis: incidence and clinical correlation with metformin serum concentration measurements. J Clin Pharm Ther 2011 Jun;36(3):376–382. PubMedGoogle Scholar
- 6.Richy FF, Sabido-Espin M, Guedes S, et al.. Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care 2014 Aug;37(8):2291–2295. PubMedGoogle Scholar
- 7.Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 2011 Feb;50(2):81–98. PubMedGoogle Scholar
- 8.Kopec KT, Kowalski MJ. Metformin-associated lactic acidosis (MALA): case files of the Einstein Medical Center medical toxicology fellowship. Journal of medical toxicology : official journal of the American College of Medical Toxicology 2013 Mar;9(1):61–66. PubMed Pubmed Central PMCID: 3576503.Google Scholar
- 9.Kim MJ, Han JY, Shin JY, et al. Metformin-associated lactic acidosis: predisposing factors and outcome. Endocrinol Metab 2015 Mar 27;30(1):78–83. PubMed Pubmed Central PMCID: 4384670.Google Scholar
- 10.Padwal RS, Gabr RQ, Sharma AM, et al. Effect of gastric bypass surgery on the absorption and bioavailability of metformin. Diabetes Care 2011 Jun;34(6):1295–1300. PubMed Pubmed Central PMCID: 3114332.Google Scholar
- 11.Cruijsen M, Koehestani P, Huttjes S, et al. Perioperative glycaemic control in insulin-treated type 2 diabetes patients undergoing gastric bypass surgery. Neth J Med 2014 May;72(4):202–209. PubMedGoogle Scholar
- 12.Aberle J, Reining F, Dannheim V, et al. Metformin after bariatric surgery—an acid problem. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2012 Mar;120(3):152–153. PubMedGoogle Scholar
- 13.Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009 May 5;150(9):604–612. PubMed Pubmed Central PMCID: 2763564.Google Scholar
- 14.Lovejoy J, Newby FD, Gebhart SS, et al. Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin. Metab Clin Exp 1992 Jan;41(1):22–27. PubMedGoogle Scholar
- 15.DiGirolamo M, Newby FD, Lovejoy J. Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1992 Apr;6(7):2405–2412. PubMedGoogle Scholar
- 16.Jansson PA, Larsson A, Smith U, et al. Lactate release from the subcutaneous tissue in lean and obese men. J Clin Invest 1994 Jan;93(1):240–246. PubMed Pubmed Central PMCID: 293758.Google Scholar
- 17.Davis TM, Jackson D, Davis WA, et al. The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: the Fremantle Diabetes Study. Br J Clin Pharmacol 2001 Aug;52(2):137–144. PubMed Pubmed Central PMCID: 2014521.Google Scholar
- 18.DeFronzo R, Fleming GA, Chen K, et al. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metab Clin Exp 2016 Feb;65(2):20–29. PubMedGoogle Scholar
- 19.Bouchoucha M, Uzzan B, Cohen R. Metformin and digestive disorders. Diabetes & metabolism 2011 Apr;37(2):90–96. PubMedGoogle Scholar