Relação entre o Tratamento com Metformina e o Desenvolvimento de Hiperlactacidemia no Serviço de Urgência

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.

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

DeFronzo

Fleming²,

Chen³

et al. 2016

Metabolism

458

333

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Risk of lactic acidosis in type 2 diabetes patients using metformin: A case control study

et al. 2018

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BackgroundMetformin constitutes first-line treatment of type 2 diabetes mellitus. It is presumed to have lactic acidosis as a dangerous, but rare, side effect.ObjectivesTo estimate the incidence rate of lactic acidosis in patients with type 2 diabetes mellitus as well as to estimate the relative risk of lactic acidosis associated with metformin treatment.MethodsThis is a population-based combined cohort and case-control study among patients with type 2 diabetes mellitus who were acutely admitted with lactic acidosis at Odense University Hospital, Denmark; in the period from 1st June 2009 to 1st October 2013. The patients included as cases were all acutely hospitalized with lactic acidosis (pH <7.35 and lactate ≥2.0 mmol/l). For each case, we identified 24 age- and sex-matched controls sampled from the same cohort with type 2 diabetes mellitus. The use of metformin identified by using a prescription database. Analyses included multivariable logistic regression and adjusting for predefined confounding: renal function, HbA1c, comorbidity and diabetes duration.ResultsOur cohort included 10,652 patients with type 2 diabetes mellitus with a median age of 74 years, and 51.5% were male. During follow-up, 163 individuals were hospitalized with lactic acidosis, corresponding to an incidence rate of 391/100,000 person years. Use of metformin was not associated with lactic acidosis: adjusted odds ratio was 0.79 (95%CI 0.54–1.17).ConclusionAmong patients with type 2 diabetes mellitus, the incidence rate of acute hospitalization with lactic acidosis was 391/100,000 person years. Use of metformin did not increase the risk of lactic acidosis. However, comorbidity seems to be an important risk factor.

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Metformin Use and Metformin-associated Lactic Acidosis in Intensive Care Unit Patients with Diabetes

Rajasurya

Anjum²,

Surani

2019

Cureus

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Metformin is a very potent anti-diabetic drug that has become the drug of choice for the treatment of type 2 diabetes. In addition to its glucose-lowering properties, it also reduces all-cause mortality through its anti-inflammatory and cardioprotective effects. Although metformin-associated lactic acidosis (MALA) is a very rare event, the mortality associated with it is close to 50%. As it is excreted through the kidney, MALA is frequently seen in patients on metformin with risk factors for developing acute kidney injury. Metformin increases the plasma lactate level in a concentration-dependent manner by inhibiting mitochondrial respiration, usually in the presence of a secondary event that disrupts lactate production or clearance. The incidence of acute kidney injury is very high in critically ill patients contributed by circulatory defects as well as contrast-induced nephropathy, the incidence of which is also high in this subset of the population. Because of this potential risk, metformin is frequently discontinued in diabetic patients admitted to the intensive care unit. Blood glucose variability and hypoglycemia, however, are both related to poor intensive care unit (ICU) outcomes and in order to prevent this in diabetic patients admitted to ICU, oral hypoglycemic agents are frequently switched to intravenous or subcutaneous insulin regimens, which allows for closer monitoring and better blood glucose control.

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Relação entre o Tratamento com Metformina e o Desenvolvimento de Hiperlactacidemia no Serviço de Urgência

Cited by 3 publications

References 17 publications

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

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

Risk of lactic acidosis in type 2 diabetes patients using metformin: A case control study

Metformin Use and Metformin-associated Lactic Acidosis in Intensive Care Unit Patients with Diabetes

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