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Erschienen in: International Urology and Nephrology 8/2016

21.04.2016 | Nephrology - Original Paper

Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease

verfasst von: Savas Sipahi, Yalcin Solak, Seyyid Bilal Acikgoz, Ahmed Bilal Genc, Mehmet Yildirim, Ulku Yilmaz, Ahmet Nalbant, Ali Tamer

Erschienen in: International Urology and Nephrology | Ausgabe 8/2016

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Abstract

Purpose

To investigate association between renal functions, lactic acid levels and acid–base balance in type 2 diabetes patients with chronic kidney disease under metformin treatment and after metformin discontinuation in a real-life setting.

Methods

A total of 65 patients with diabetes (mean age 68.5 ± 8.9 years, 56.9 % females) in whom metformin treatment was discontinued due to reduced glomerular filtration rate (GFR) were included in this retrospective study. Data on patient demographics, metformin treatment and laboratory findings on the last day of metformin treatment and 2–3 weeks after metformin discontinuation including blood lactate and creatinine, estimated glomerular filtration rate (eGFR) and acid–base balance measurements in blood [pH, bicarbonate, base excess] were collected from medical records. The correlation of lactate levels with eGFR, blood pH and creatinine levels and changes in laboratory findings after metformin discontinuation were evaluated.

Results

Before metformin discontinuation, hyperlactatemia was observed in 78.5 % of patients and metabolic acidosis in 36.9 % of patients, but none had lactic acidosis. Patients with normolactatemia and hyperlactatemia were similar in terms of metformin dosage and laboratory parameters. Lactate levels were not significantly correlated with serum creatinine (r = −0.14; p = 0.263) and eGFR (r = 0.11, p = 0.374). After metformin discontinuation, a significant decrease was observed in median lactate levels (from 2.20 to 1.85 mmol/L; p = 0.002).

Conclusion

In conclusion, our findings support the low risk of MALA among patients with mild-to-moderate renal impairment and the likelihood of metformin to be an innocent bystander without a pathogenic role in the lactic acidosis in most cases.
Literatur
1.
Zurück zum Zitat Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35:1364–1379CrossRefPubMedPubMedCentral Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35:1364–1379CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat UK Prospective Diabetes Study (UKPDS) Group (1998) Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865CrossRef UK Prospective Diabetes Study (UKPDS) Group (1998) Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865CrossRef
3.
Zurück zum Zitat Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R et al (2009) American Diabetes Association; European Association for the Study of Diabetes. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 52:17–30CrossRefPubMed Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R et al (2009) American Diabetes Association; European Association for the Study of Diabetes. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 52:17–30CrossRefPubMed
4.
Zurück zum Zitat Bennett WL, Maruthur NM, Singh S, Segal JB, Wilson LM, Chatterjee R et al (2011) Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 154:602–613CrossRefPubMedPubMedCentral Bennett WL, Maruthur NM, Singh S, Segal JB, Wilson LM, Chatterjee R et al (2011) Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 154:602–613CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Kajbaf F, Arnouts P, de Broe M, Lalau JD (2013) Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world. Pharmacoepidemiol Drug Saf 10:1027–1035 Kajbaf F, Arnouts P, de Broe M, Lalau JD (2013) Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world. Pharmacoepidemiol Drug Saf 10:1027–1035
6.
Zurück zum Zitat Misbin RI, Green L, Stadel BV, Gueriguian JL, Gabbi A, Fleming GA (1998) Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338:265–266CrossRefPubMed Misbin RI, Green L, Stadel BV, Gueriguian JL, Gabbi A, Fleming GA (1998) Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338:265–266CrossRefPubMed
7.
Zurück zum Zitat Fall PJ, Szerlip HM (2005) Lactic acidosis: from sour milk to septic shock. J Intensive Care Med 20:255–271CrossRefPubMed Fall PJ, Szerlip HM (2005) Lactic acidosis: from sour milk to septic shock. J Intensive Care Med 20:255–271CrossRefPubMed
8.
Zurück zum Zitat DeFronzo R, Fleming AG, Chenc K, Bicsak TA (2016) Metformin-associated lactic acidosis: current perspectives on causes and risk. Metab. Clin Exp 65:20–29CrossRefPubMed DeFronzo R, Fleming AG, Chenc K, Bicsak TA (2016) Metformin-associated lactic acidosis: current perspectives on causes and risk. Metab. Clin Exp 65:20–29CrossRefPubMed
9.
Zurück zum Zitat Lalau JD (2010) Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf 33:727–740CrossRefPubMed Lalau JD (2010) Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf 33:727–740CrossRefPubMed
10.
Zurück zum Zitat Scheen AJ, Paquot N (2013) Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes. Diabetes Metab 39:179–190 (Review) CrossRefPubMed Scheen AJ, Paquot N (2013) Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes. Diabetes Metab 39:179–190 (Review) CrossRefPubMed
13.
Zurück zum Zitat Lemyze M, Mallat J, Thevenin D (2011) Metformin-associated lactic acidosis: Is it really just an association? Am J Emerg Med 29:349–350CrossRefPubMed Lemyze M, Mallat J, Thevenin D (2011) Metformin-associated lactic acidosis: Is it really just an association? Am J Emerg Med 29:349–350CrossRefPubMed
14.
Zurück zum Zitat Juurlink DN, Roberts DM (2014) The enigma of metformin-associated lactic acidosis. Clin Toxicol (Philadelphia, Pa) 52:85–87CrossRef Juurlink DN, Roberts DM (2014) The enigma of metformin-associated lactic acidosis. Clin Toxicol (Philadelphia, Pa) 52:85–87CrossRef
15.
Zurück zum Zitat Adam WR, O’Brien RC (2014) A justification for less restrictive guidelines on the use of metformin in stable chronic renal failure. Diabet Med 31:1032–1038 (Review) CrossRefPubMed Adam WR, O’Brien RC (2014) A justification for less restrictive guidelines on the use of metformin in stable chronic renal failure. Diabet Med 31:1032–1038 (Review) CrossRefPubMed
16.
Zurück zum Zitat Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV (2005) Comparative outcomes study of metformin intervention versus conventional approach the COSMIC approach study. Diabetes Care 28:539–543CrossRefPubMed Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV (2005) Comparative outcomes study of metformin intervention versus conventional approach the COSMIC approach study. Diabetes Care 28:539–543CrossRefPubMed
17.
Zurück zum Zitat Salpeter SR, Greyber E, Pasternak GA, Salpeter EE (2010) Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 1:CD002967PubMed Salpeter SR, Greyber E, Pasternak GA, Salpeter EE (2010) Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 1:CD002967PubMed
18.
Zurück zum Zitat Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR (2008) Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case–control analysis. Diabetes Care 31:2086–2091CrossRefPubMedPubMedCentral Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR (2008) Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case–control analysis. Diabetes Care 31:2086–2091CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE et al (2008) Metformin-associated lactic acidosis in an intensive care unit. Crit Care 12:R149CrossRefPubMedPubMedCentral Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE et al (2008) Metformin-associated lactic acidosis in an intensive care unit. Crit Care 12:R149CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Almirall J, Briculle M, Gonzalez-Clemente JM (2008) Metformin associated lactic acidosis in type 2 diabetes mellitus: incidence and presentation in common clinical practice. Nephrol Dial Transpl 23:2436–2438CrossRef Almirall J, Briculle M, Gonzalez-Clemente JM (2008) Metformin associated lactic acidosis in type 2 diabetes mellitus: incidence and presentation in common clinical practice. Nephrol Dial Transpl 23:2436–2438CrossRef
21.
Zurück zum Zitat Richy FF, Sabido-Espin M, Guedes S, Corvino FA, Gottwald-Hostalek U (2014) Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care 37:2291–2295CrossRefPubMed Richy FF, Sabido-Espin M, Guedes S, Corvino FA, Gottwald-Hostalek U (2014) Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care 37:2291–2295CrossRefPubMed
22.
Zurück zum Zitat Salpeter SR, Greyber E, Pasternak GA, Salpeter EE (2010) Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 4:CD002967PubMed Salpeter SR, Greyber E, Pasternak GA, Salpeter EE (2010) Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 4:CD002967PubMed
23.
Zurück zum Zitat Seidowsky A, Nseir S, Houdret N, Fourrier F (2009) Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med 37:2191–2196CrossRefPubMed Seidowsky A, Nseir S, Houdret N, Fourrier F (2009) Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med 37:2191–2196CrossRefPubMed
24.
Zurück zum Zitat Arroyo D, Melero R, Panizo N, Goicoechea M, Rodríguez-Benítez P, Vinuesa SG et al (2011) Metformin-associated acute kidney injury and lactic acidosis. Int J Nephrol 2011:749653CrossRefPubMedPubMedCentral Arroyo D, Melero R, Panizo N, Goicoechea M, Rodríguez-Benítez P, Vinuesa SG et al (2011) Metformin-associated acute kidney injury and lactic acidosis. Int J Nephrol 2011:749653CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Hanatani T, Sai K, Tohkin M, Segawa K, Saito Y (2015) Impact of Japanese regulatory action on metformin-associated lactic acidosis in type II diabetes patients. Int J Clin Pharm 37:537–545CrossRefPubMed Hanatani T, Sai K, Tohkin M, Segawa K, Saito Y (2015) Impact of Japanese regulatory action on metformin-associated lactic acidosis in type II diabetes patients. Int J Clin Pharm 37:537–545CrossRefPubMed
28.
Zurück zum Zitat Goldberg T, Kroehl ME, Suddarth KH, Trinkley KE (2015) Variations in Metformin prescribing for type 2 Diabetes. J Am Board Fam Med 28:777–784CrossRefPubMed Goldberg T, Kroehl ME, Suddarth KH, Trinkley KE (2015) Variations in Metformin prescribing for type 2 Diabetes. J Am Board Fam Med 28:777–784CrossRefPubMed
29.
Zurück zum Zitat Philbrick AM, Ernst ME, McDanel DL, Ross MB, Moores KG (2009) Metformin use in renal dysfunction: is a serum creatinine threshold appropriate? Am J Health Syst Pharm 66:2017–2023CrossRefPubMed Philbrick AM, Ernst ME, McDanel DL, Ross MB, Moores KG (2009) Metformin use in renal dysfunction: is a serum creatinine threshold appropriate? Am J Health Syst Pharm 66:2017–2023CrossRefPubMed
30.
Zurück zum Zitat Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 130:461–470CrossRefPubMed Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 130:461–470CrossRefPubMed
31.
Zurück zum Zitat Pongwecharak J, Tengmeesri N, Malanusorn N, Panthong M, Pawangkapin N (2009) Prescribing metformin in type 2 diabetes with a contraindication: prevalence and outcome. Pharm World Sci 31:481–486CrossRefPubMed Pongwecharak J, Tengmeesri N, Malanusorn N, Panthong M, Pawangkapin N (2009) Prescribing metformin in type 2 diabetes with a contraindication: prevalence and outcome. Pharm World Sci 31:481–486CrossRefPubMed
32.
Zurück zum Zitat Huang W, Castelino RL, Peterson GMJ (2015) Adverse event notifications implicating metformin with lactic acidosis in Australia. Diabetes Complicat. 29:1261–1265CrossRef Huang W, Castelino RL, Peterson GMJ (2015) Adverse event notifications implicating metformin with lactic acidosis in Australia. Diabetes Complicat. 29:1261–1265CrossRef
33.
Zurück zum Zitat Kajbaf F, Lalau JD (2013) The criteria for metformin-associated lactic acidosis: the quality of reporting in a large pharmacovigilance database. Diabet Med 30:345–348CrossRefPubMed Kajbaf F, Lalau JD (2013) The criteria for metformin-associated lactic acidosis: the quality of reporting in a large pharmacovigilance database. Diabet Med 30:345–348CrossRefPubMed
34.
Zurück zum Zitat Luft D, Deichsel G, Schmulling R, Stein N, Eggstein M (1983) Definition of clinically relevant lactic acidosis in patients with internal diseases. Am J Clin Pathol 80:484–489CrossRefPubMed Luft D, Deichsel G, Schmulling R, Stein N, Eggstein M (1983) Definition of clinically relevant lactic acidosis in patients with internal diseases. Am J Clin Pathol 80:484–489CrossRefPubMed
35.
Zurück zum Zitat Salpeter S, Greyber E, Pasternak G, Salpeter E (2003) Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2:CD002967PubMed Salpeter S, Greyber E, Pasternak G, Salpeter E (2003) Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2:CD002967PubMed
36.
Zurück zum Zitat Lalau J, Lacroix C (2003) Measurement of metformin concentration in erythro-cytes: clinical implications. Diabetes Obes Metab 5:92–98CrossRef Lalau J, Lacroix C (2003) Measurement of metformin concentration in erythro-cytes: clinical implications. Diabetes Obes Metab 5:92–98CrossRef
37.
Zurück zum Zitat Davis TM, Jackson D, Davis WA, Bruce DG, Chubb P (2001) The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: the Fremantle Diabetes Study. Br J Clin Pharmacol 52:137–144CrossRefPubMedPubMedCentral Davis TM, Jackson D, Davis WA, Bruce DG, Chubb P (2001) The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: the Fremantle Diabetes Study. Br J Clin Pharmacol 52:137–144CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Emslie-Smith AM, Boyle DI, Evans JM, Sullivan F, Morris AD (2001) DARTS/MEMO collaboration. Contraindications to metformin therapy in patients with type 2 diabetes- a population-based study of adherence to prescribing guidelines. Diabet Med 18:483–488CrossRefPubMed Emslie-Smith AM, Boyle DI, Evans JM, Sullivan F, Morris AD (2001) DARTS/MEMO collaboration. Contraindications to metformin therapy in patients with type 2 diabetes- a population-based study of adherence to prescribing guidelines. Diabet Med 18:483–488CrossRefPubMed
39.
Zurück zum Zitat Mathieu C (2015) Metformin-associated lactic acidosis: time to let it go? J Diabetes Complicat. 29:974–975CrossRefPubMed Mathieu C (2015) Metformin-associated lactic acidosis: time to let it go? J Diabetes Complicat. 29:974–975CrossRefPubMed
40.
Zurück zum Zitat Rachmani R, Slavacheski I, Levi Z, Zadok B, Kedar Y, Ravid M (2002) Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 13:428–433CrossRefPubMed Rachmani R, Slavacheski I, Levi Z, Zadok B, Kedar Y, Ravid M (2002) Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 13:428–433CrossRefPubMed
41.
Zurück zum Zitat Stades AME, Heikens JT, Erkelens DW, Holleman F, Hoekstra JB (2004) Metformin and lactic acidosis: cause or coincidence? A review of case reports. J Intern Med 255:179–187CrossRefPubMed Stades AME, Heikens JT, Erkelens DW, Holleman F, Hoekstra JB (2004) Metformin and lactic acidosis: cause or coincidence? A review of case reports. J Intern Med 255:179–187CrossRefPubMed
42.
Zurück zum Zitat Scale T, Harvey JN (2011) Diabetes, metformin and lactic acidosis. Clin Endocrinol (Oxf) 74:191–196CrossRef Scale T, Harvey JN (2011) Diabetes, metformin and lactic acidosis. Clin Endocrinol (Oxf) 74:191–196CrossRef
43.
Zurück zum Zitat van Berlo-van de Laar IR, Vermeij CG, Doorenbos CJ (2011) Metformin associated lactic acidosis: incidence and clinical correlation with metformin serum concentration measurements. J Clin Pharm Ther 36:376–382CrossRefPubMed van Berlo-van de Laar IR, Vermeij CG, Doorenbos CJ (2011) Metformin associated lactic acidosis: incidence and clinical correlation with metformin serum concentration measurements. J Clin Pharm Ther 36:376–382CrossRefPubMed
44.
Zurück zum Zitat Duong JK, Kumar SS, Kirkpatrick CM, Greenup LC, Arora M, Lee TC et al (2013) Population pharmacokinetics of metformin in healthy subjects and patients with type 2 diabetes mellitus: simulation of doses according to renal function. Clin Pharmacokinet 52:373–384CrossRefPubMed Duong JK, Kumar SS, Kirkpatrick CM, Greenup LC, Arora M, Lee TC et al (2013) Population pharmacokinetics of metformin in healthy subjects and patients with type 2 diabetes mellitus: simulation of doses according to renal function. Clin Pharmacokinet 52:373–384CrossRefPubMed
45.
Zurück zum Zitat Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK (2014) Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA 312:2668–2675CrossRefPubMedPubMedCentral Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK (2014) Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA 312:2668–2675CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Lalau JD, Race JM (2001) Lactic acidosis in metformin therapy: searching for a link with metformin in reports of ‘metformin-associated lactic acidosis’. Diabetes Obes Metab 3:195–201CrossRefPubMed Lalau JD, Race JM (2001) Lactic acidosis in metformin therapy: searching for a link with metformin in reports of ‘metformin-associated lactic acidosis’. Diabetes Obes Metab 3:195–201CrossRefPubMed
Metadaten
Titel
Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease
verfasst von
Savas Sipahi
Yalcin Solak
Seyyid Bilal Acikgoz
Ahmed Bilal Genc
Mehmet Yildirim
Ulku Yilmaz
Ahmet Nalbant
Ali Tamer
Publikationsdatum
21.04.2016
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 8/2016
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-016-1288-x

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