Gastrointestinal adverse effects including anorexia, nausea, vomiting, and diarrhea may occur with biguanides; patients may experience taste disturbance and there may be weight loss. Absorption of various substances including vitamin Bi, may be impaired. Skin reactions have been reported rarely. Hypoglycemia is rare with a biguanide given alone, although it may occur if other contributing factors or drugs are present. Lactic acidosis, sometimes fatal, has occurred with biguanides, primarily with phenformin. When it has occurred with metformin most cases have been in patients whose condition contra-indicated the use of the drug, particularly those with renal impairment. Phenformin has been implicated in the controversial reports of excessive cardiovascular mortality associated with oral hypoglycemic therapy.