Gastrointestinal adverse effects including anorexia,nausea, vomiting, and diarrhoea may occur with biguanides;patients may experience taste disturbance andthere may be weight loss. Absorption of various substancesincluding vitamin B12 may be impaired. Skinreactions have been reported rarely.Hypoglycaemia is rare with a biguanide given alone,although it may occur if other contributing factors ordrugs are present.Lactic acidosis, sometimes fatal, has occurred withbiguanides, primarily with phenformin. When it hasoccurred with metformin most cases have been in patientswhose condition contra-indicated the use of thedrug, particularly those with renal impairment.Phenformin has been implicated in the controversialreports of excessive cardiovascular mortality associatedwith oral hypoglycaemic therapyEffects on the blood. Megaloblastic anaemia has occurredwith biguanide therapy (see Malabsorption, under Effects on theGastrointestinal Tract, below). A few cases of metformininducedhaemolysis resulting in hyperbilirubinaemia and jaundicehave also been describedEffects on the gastrointestinal tract. DIARRHOEA. In a retrospectivesurvey, 30 of 265 diabetic patients reported diarrhoeaor alternating diarrhoea and constipation, comprising:11 of 54 taking metformin; 9 of 45 taking metformin with asulfonylurea; 3 of 53 taking a sulfonylurea only; 5 of 78 oninsulin therapy; 2 of 35 on diet alone. Among 150 nondiabeticcontrols reported diarrhoea. Chronic diarrhoea describedas watery, often explosive, and frequently causing faecal incontinence,has been reported as an adverse effect of late onsetin patients receiving metformin. Some patients had beenon stable metformin therapy for several years before the onsetof diarrhoea. Symptoms ceased upon withdrawal of metformin,and recurred in cases of rechallenge
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