How metformin causes lactic acidosis

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  1. sergeyef Moderator

    How 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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    Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear. They usually occur. Metabolic acidosis is a condition that occurs when the body produces excessive quantities of acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e. blood pH is low less than 7.35 due to increased production of hydrogen ions by the body or the inability of the body to form bicarbonate HCO 3 − in the kidney. Oct 30, 2015. MALA should likely be categorized into separate entities 1 acute overdoses associated with lactic acidosis 2 those with underlying causes for.

    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.

    How metformin causes lactic acidosis

    Metformin hydrochloride - Drug Summary - PDR. Net, Metabolic acidosis - Wikipedia

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  6. HISTORICAL PERSPECTIVE. Despite these proven benefits, metformin remains contraindicated in a large segment of the type 2 diabetic population, largely because of concerns over the rare adverse effect of lactic acidosis.

    • Use of Metformin in the Setting of Mild-to-Moderate Renal..
    • MALA Metformin-Associated Lactic Acidosis California Poison..
    • Metformin-associated Lactic Acidosis MALA - Life in the Fast Lane.

    Metformin causes general GI tract upset and nausea and vomiting is a part of it. Unfortunately, as many as 26% of patients report nausea and vomiting as two of metformin side effects. Metformin may rarely cause a serious, life-threatening condition called lactic acidosis. Tell your doctor if you have kidney disease. Your doctor will probably tell you not to take metformin. 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.

     
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