Why metformin causes lactic acidosis

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    Why metformin causes lactic acidosis


    Metformin, a dimethylbiguanide, is a widely used oral antihyperglycaemic drug used in the long term treatment of type 2 diabetes mellitus. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome. Many large studies have shown that intensive glucose control with metformin in overweight patients with type 2 diabetes is associated with risk reductions of 32% (P=0.002) for any diabetes related end point, 42% (P=0.017) for diabetes related death, and 36% (P=0.011) for all cause mortality compared with diet alone. Furthermore, metformin reduces microvascular end points, and its degree of glycaemic control is similar to that sulphonylureas and insulin. Metformin is considered to be first line treatment in overweight patients with type 2 diabetes whose blood glucose is inadequately controlled by lifestyle interventions alone and should be considered as a first line glucose lowering treatment in non-overweight patients with type 2 diabetes because of its other beneficial effects. It may also be useful in overweight patients with type 1 diabetes. A potential complication of metformin is the development of type B (non-hypoxic) lactic acidosis. In order to use Medscape, your browser must be set to accept cookies delivered by the Medscape site. Medscape uses cookies to customize the site based on the information we collect at registration. The cookies contain no personally identifiable information and have no effect once you leave the Medscape site.

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    Jan 19, 2010. The risk for lactic acidosis associated with metformin use may be. aerobic metabolism and causes increased metabolism of pyruvate to lactate. The labeling of Glucophage reflected a belief that metformin had the potential to cause lactic acidosis, but that the risk could be mitigated by careful selection of. To describe a case of metformin-associated lactic acidosis. who had no obvious risks for lactic acidosis eg, re-. phenfonnin cause lactic acidosis is uncertain.

    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. Metformin is a useful anti-hyperglycaemic agent but significant mortality is associated with drug-induced lactic acidosis. Significant renal and hepatic disease, alcoholism and conditions associated with hypoxia (eg. cardiac and pulmonary disease, surgery) are contraindications to the use of metformin. Other risk factors for metformin-induced lactic acidosis are sepsis, dehydration, high dosages and increasing age. Metformin remains a major reported cause of drug-associated mortality in New Zealand. Of the 12 cases of lactic acidosis associated with metformin reported to CARM since 1977, 2 occurred in the last year and 8 cases had a fatal outcome. Metformin is a useful therapeutic agent for obese non-insulin dependent diabetics and those whose glycaemia cannot be controlled by sulphonylurea monotherapy.

    Why metformin causes lactic acidosis

    Metformin-associated Lactic Acidosis MALA - Life in the Fast Lane, The Phantom of Lactic Acidosis due to Metformin in Patients With.

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  4. Jun 6, 2018. According to results of a recent combined cohort and case-control study, the incidence rate of acute hospitalization due to lactic acidosis in.

    • Does Metformin Use Increase the Risk for Lactic Acidosis in T2D..
    • Metformin-Associated Lactic Acidosis - Journal of the American Board..
    • Spotlight A case of Metformin Associated Lactic Acidosis – Clinical..

    Although metformin is a very rare cause of lactic acidosis, it is almost invariably very severe. Curiously, however, as a recently published study has confirmed. Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear. They usually occur. Patients with extreme lactic metabolic acidosis caused by metformin can survive when CVVH treatment is initiated rapidly. intercurrent symptoms or diseases.

     
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