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Hence, it is probable that the accumulation of lactic acid in the colon might result in all or some of the GI side effects of metformin, particularly in users that consume diets high in sugars and starch

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The methodologic design of the rescue arm favors the sq methotrexate group, in that, on average, approximately 10% of the subjects in this group received a 25% higher dose of methotrexate than did those in the oral group (who could never receive a dose higher than 15 mg as part of the protocol)