Yonsei Med J.  2017 Mar;58(2):312-318. 10.3349/ymj.2017.58.2.312.

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

• Lee EY
• Hwang S
• Lee YH
• Lee SH
• Lee YM
• Kang HP
• Han E
• Lee W
• Lee BW
• Kang ES
• Cha BS
• Lee HC

• KMID: 2427119
• DOI: http://doi.org/10.3349/ymj.2017.58.2.312

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 patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no 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.

Keyword

Metformin; lactic acidosis; diabetes mellitus; lactate

MeSH Terms

Acidosis, Lactic/blood/*chemically induced/epidemiology
Adult
Aged
Cross-Sectional Studies
Diabetes Mellitus, Type 2/blood/*drug therapy/epidemiology
Female
Humans
Hyperlactatemia/blood/*chemically induced/epidemiology
Hypoglycemic Agents/*adverse effects/blood/therapeutic use
Incidence
Lactic Acid/blood
Male
Metformin/*adverse effects/blood/therapeutic use
Middle Aged
Prevalence
Regression Analysis
Renal Insufficiency/epidemiology/physiopathology
Risk Factors
Hypoglycemic Agents
Lactic Acid
Metformin

Figure

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  Fig. 1 Flow diagram of the study population.

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  Fig. 2 Odds ratio for the development of lactic acidosis in subgroup with hyperlactatemia. The odds ratio of eGFR was expressed as an increased risk per 10 mL/min/1.73 m2 increase of eGFR. ALT, alanine aminotransferase; BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin.

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