Metformin-Associated Lactic Acidosis: Predisposing Factors and Outcome

Kim, Min Ju; Han, Ju Young; Shin, Junyoung; Kim, Shin Il; Lee, Jeong Min; Hong, Seongbin; Kim, So Hun; Nam, Moon Suk; Kim, Yong Seong

doi:10.3803/enm.2015.30.1.78

Cited by 35 publications

(28 citation statements)

References 18 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other studies have also shown that metformin concentrations remain in a therapeutic range in mildly to moderately renal impaired patients [40]. At the same time, growing evidence suggests that the underlying disease associated with the tissue hypoxia rather than metformin use is related to lactic acidosis in diabetes [41][42][43]. In the present research, no case of lactic acidosis was observed during hospitalization for both groups.…”

Section: Discussionsupporting

confidence: 60%

Effect of continuous use of metformin on kidney function in diabetes patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Zhu

Liu

2020

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background: Diabetes patients presenting with ST-segment elevation myocardial infarction (STEMI) scheduled for primary percutaneous coronary intervention (PCI) have an increased risk of contrast induced-acute kidney injury (CI-AKI). The effects of continuous use of metformin on kidney function are still controversial in patients submitted to primary PCI. This study aimed to assess continuous metformin therapy on kidney function in diabetic patients undergoing coronary intervention. Methods: Two hundred eighty-four patients with metformin-treated diabetes, who underwent coronary intervention within 24 h for STEMI, were enrolled in the retrospective study. All the patients had estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m 2 . According to the physicians' decisions after admission, 119 patients continued metformin treatment after primary PCI, while 165 patients discontinued it > 48 h after the procedure. Serum creatinine was collected at admission and within 48 h post primary PCI to evaluate the incidence of CI-AKI. We performed a multiple logistic regression analysis to examine the determinants of CI-AKI. Results: No statistical difference in CI-AKI incidence between the continuous and the discontinuous metformin group (12.6%vs10.3%, p = 0.545). Multivariable logistic regression analysis indicated eGFR ≤60 ml/min/1.73 m 2 [p = 0.025, OR: 3.131; 95% CI (1.156-8.482)] and contrast volume [p = 0.002, OR: 1.010; 95% CI (1.004-1.016)] were predictive factors of CI-AKI. Metformin therapy was irrelevant to CI-AKI [p = 0.365, OR: 0.698; 95% CI (0.320-1.521)]. No case of lactic acidosis was found in this study. Besides, the study supported discontinuation of metformin was not beneficial for patients' blood glucose control after admission. Conclusions: The study indicated that the metformin continuation after primary PCI for STEMI in diabetic patients with eGFR > 30 ml/min / 1.73 m 2 did not increase the risk of CI-AKI.

show abstract

Section: Discussionsupporting

confidence: 60%

Effect of continuous use of metformin on kidney function in diabetes patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Zhu

Liu

2020

BMC Cardiovasc Disord

View full text Add to dashboard Cite

show abstract

“…Owing to the multiple and often nonspecific signs and symptoms of MALA, as well as the potential impact of other conditions and medications that can predispose a patient to lactic acidosis, MALA can be difficult to predict or diagnose [21][22][23]. This is true especially in the absence of knowing the circulating metformin concentration in a patient presenting with symptoms [24]. However, it is known that MALA occurs when there is an imbalance between increased lactate production and impaired metabolism/reduced clearance.…”

Section: Risk Factors For Malamentioning

confidence: 99%

Metformin-associated lactic acidosis: Current perspectives on causes and risk

DeFronzo

Fleming²,

Chen³

et al. 2016

Metabolism

479

333

View full text Add to dashboard Cite

Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.

show abstract

“…In addition, a majority of the patients reported have comorbidities that could contribute to hyperlactatemia. Renal impairment is the most common comorbidity reported in cases of MALA [5,10,18,25,[42][43][44]]. This has led to significant research regarding the safety of metformin use in patients with chronic kidney disease.…”

Section: Discussionmentioning

confidence: 99%