Association between Metformin Use and Risk of Lactic Acidosis or Elevated Lactate Concentration in Type 2 Diabetes

다국어 초록 (Multilingual Abstract)

Purpose: Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes.
Materials and Methods: This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007–2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m2. Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35.
Results: Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m2. Most patientswith lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicatedno association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327–15.965)].
Conclusion: Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.

참고문헌 (Reference)

1 Lalau JD, "Role of metformin accumulation in metformin-associated lactic acidosis" 18 : 779-784, 1995

2 Salpeter SR, "Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus" (4) : CD002967-, 2010

3 Min Ju Kim, "Metformin-Associated Lactic Acidosis: Predisposing Factors and Outcome" 대한내분비학회 30 (30): 78-83, 2015

4 서성환, "Metformin-Associated Lactic Acidosis" 대한내분비학회 30 (30): 45-46, 2015

5 Bodmer M, "Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis" 31 : 2086-2091, 2008

6 Duong JK, "Metformin therapy in patients with chronic kidney disease" 14 : 963-965, 2012

7 Stades AM, "Metformin and lactic acidosis: cause or coincidence? A review of case reports" 255 : 179-187, 2004

8 김동림, "Metformin Based Dual-Combination Therapies in Drug Naïve Type 2 Diabetic Patients" 대한당뇨병학회 37 (37): 429-432, 2013

9 Bailey CJ, "Metformin" 334 : 574-579, 1996

10 Cusi K, "Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus" 81 : 4059-4067, 1996

11 Stumvoll M, "Metabolic effects of metformin in non-insulin-dependent diabetes mellitus" 333 : 550-554, 1995

12 Velussi M, "Median-term (4months) treatment with glibenclamide + metformin substituting for glibenclamide + fenformin lowers the lacticemia levels in type-2 diabetics (NIDDM)" 141 : 483-492, 1992

13 Inzucchi SE, "Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes" 38 : 140-149, 2015

14 Brown JB, "Lactic acidosis rates in type 2 diabetes" 21 : 1659-1663, 1998

15 Lalau JD, "Lactic acidosis in metformin-treated patients. Prognostic value of arterial lactate levels and plasma metformin concentrations" 20 : 377-384, 1999

16 Searle GL, "Lactic acidosis associated with phenformin therapy. Evidence that inhibited lactate oxidation is the causative factor" 24 : 741-745, 1975

17 Kreisberg RA, "Lactate turnover and gluconeogenesis in obesity. Effect of phenformin" 19 : 64-69, 1970

18 Lim VC, "Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal function" 61 : 1829-1833, 2007

19 Stang M, "Incidence of lactic acidosis in metformin users" 22 : 925-927, 1999

20 Bergman U, "Epidemiology of adverse drug reactions to phenformin and metformin" 2 : 464-466, 1978

21 DeFronzo RA, "Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group" 333 : 541-549, 1995

22 UK Prospective Diabetes Study (UKPDS) Group, "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)" 352 : 854-865, 1998

23 Pilger E, "Effect of biguanide therapy on lactate metabolism during graded submaximal ergometric testing" 5 : 91-95, 1978

24 Scale T, "Diabetes, metformin and lactic acidosis" 74 : 191-196, 2011

25 Gan SC, "Biguanide-associated lactic acidosis. Case report and review of the literature" 152 : 2333-2336, 1992

26 Dell’Aglio DM, "Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors:a systematic review of the literature" 54 : 818-823, 2009

27 Levey AS, "A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group" 130 : 461-470, 1999