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Page: Adverse Effects
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Lactic acidosis
The most serious side effect of metformin is lactic acidosis; this complication is rare if the contra-indications are followed, as it seems limited to those with impaired liver or kidney function.
Phenformin, another biguanide, was withdrawn because of an increased risk of lactic acidosis (up to 60 cases per million patient-years). However, metformin is safer and the risk of developing lactic acidosis is not changed by the medication, so long as it is not prescribed to the known high-risk groups.
Gastrointestinal
The most common side effect of metformin is gastrointestinal upset, including diarrhea, cramps, nausea and vomiting. In a clinical trial of 286 subjects, 53.2% of the 141 who were given Metformin IR (as opposed to placebo) reported diarrhea, versus 11.7% for placebo, and 25.5% reported nausea/vomiting, versus 8.3% for those on placebo.
Gastrointestinal upset can cause severe discomfort for patients; it is most common when metformin is first administered, or when the dose is increased. The discomfort can often be avoided by beginning at a low dose (1 to 1.7 grams per day) and increasing the dose gradually. Gastrointestinal upset after prolonged, steady use is less common.
Long-term use of metformin has been associated with increased homocysteine levels and malabsorption of vitamin B12. Higher doses and prolonged use are associated with increased incidence of B12 deficiency, and some researchers recommend screening or prevention strategies.
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