People with kidney disease (diabetic nephropathy) should not use biguanides. They are at increased risk of developing a buildup of lactic acid in the blood (lactic acidosis). This is the most serious side effect associated with biguanides and is potentially life-threatening. Other forms of metabolic acidosis, including acute or chronic diabetic ketoacidosis, also rule out use of metformin, according to the FDA.

A physician should test the kidney function of candidates for biguanide therapy. This can be done using a blood test called the serum creatinine, or a urine test.

Symptoms of lactic acidosis include:

• Weakness or fatigue
• Unusual muscle pain
• Stomach discomfort

Liver disease, heart failure and alcohol abuse (including sporadic episodes of “binge” drinking) all can trigger lactic acidosis. Patients with a history of those conditions may not be good candidates for biguanide therapy. Recent research suggests that metformin may benefit some diabetic patients with heart failure, but the FDA cautions against prescribing it for people with congestive heart failure.

Dehydration also raises the risk of acidosis, so patients should talk to their physician about ways to keep hydrated in all circumstances.

Patients who are having surgery or medical tests that use dye, such as barium x-rays, should inform their physician of their use of biguanides. The dyes can impair kidney function, causing the drug to build up in the blood. Patients may be advised to suspend their use of these medications for a period of time.

Other conditions that may affect use of biguanides include:

• Severe injury, infection or burns
  
  
• High fever
  
  
• Ketosis, a buildup of ketones (waste products produced when the body burns fat for energy instead of glucose
  
  
• Vomiting, severe diarrhea, slow stomach emptying (gastroparesis) or any other condition that impedes consumption or absorption of food
  
  
• Conditions that cause low glucose (hypoglycemia) or rapid changes in glucose
  
  
• Female hormone changes during puberty, pregnancy or menstruation
  
  
• Overactive or underactive adrenal glands (e.g., Cushing's syndrome or Addison's disease
  
  
• Overactive or or underactive thyroid gland (hyperthyroidism or hypothyroidism)
  
  
• Underactive pituitary gland (hypopituitarism)
  
  
• Major surgery
  
  
• Disorders of the heart or blood vessels
  
  
• Weakened or malnourished physical condition
  
  
• Severe mental stress