"Metformin, however, can cause lactic acidosis in conditions where lactic acid production is high and the disposal of lactic acid is reduced. Moreover, metformin increases lactate oxidation and does not increase the release of lactate from muscle, unlike phenformin. It is a less powerful inhibitor of mitochondrial respiration, which is probably the main reason for its decreased risk of lactic acidosis compared with phenformin's and buformin's. James highlights: "There are many reasons why metformin causes less lactic acidosis than phenformin. Metformin has about 24 times less reported incidents of lactic acidosis compared with phenformin. Metformin use started in France in 1957, but it was not introduced in the United States until 1995, nearly 20 years after the biguanide phenformin was taken off the market because of its risk of lactic acidosis, which was often fatal." "Another concern about metformin is the potential for lactic acidosis. Slow-release metformin does not cause a rapid increase in the blood metformin levels, and a similar effect may occur when taking metformin during a meal. The exact reasons for the gastrointestinal adverse effects are not fully understood, but there is evidence that local serotonin production may be stimulated by metformin in the gut. Nair explains: "These symptoms are more likely to occur when patients ingest metformin on an empty stomach and may be mitigated by taking metformin in the middle of the meal or using a sustained-release formulation. Metformin's most common side effect is gastrointestinal distress, which includes nausea, diarrhea and upper abdominal discomfort.ĭr. This beneficial effect may be in part due to a modest effect of metformin on reducing blood pressure (unrelated to weight loss), improving lipid profiles (especially triglycerides) and endothelial function, reducing fibrinogen levels, and possibly increasing fibrinolysis." Although there are conflicting reports, metformin may reduce the risk of cardiovascular events, especially in patients with T2DM who are overweight. "Some reports indicate that metformin is associated with preferential fat loss, and it may impart mild anorexic effects via its hypothalamic actions. Another advantage is that, unlike hypoglycemic agents such as sulfonylureas or insulin, metformin treatment is not associated with weight gain, but may cause modest weight loss. James, M.D., an endocrine trainee in Endocrinology, Diabetes, Metabolism & Nutrition at Mayo Clinic's campus in Minnesota, notes: "One of its major advantages is that metformin does not cause significant hypoglycemia. Metformin is a highly desirable therapy for T2DM for a number of reasons. Currently, over 150 million people worldwide are using metformin." "In women with polycystic ovarian syndrome, metformin is effective not only at improving insulin sensitivity, but also in enhancing their potential for fertility.
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