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Lactic acidosis: Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin accumulation. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. The incidence of lactic acidosis can and should be reduced by assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.
Diagnosis: The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps with digestive disorders as abdominal pain and severe asthenia.
This can be followed by acidotic dyspnea, abdominal pain, hypothermia and coma.
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, metformin should be discontinued and the patient should be hospitalised immediately.
Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter: at least annually in patients with normal renal function, at least two to four times a year in patients with creatinine clearance levels at the limit of normal and in elderly subjects.
Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID).
Administration of iodinated contrast media: The intravascular administration of iodinated contrast media in radiological studies can lead to renal failure. This may lead to metformin accumulation and risk of lactic acidosis. Metformin must be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Surgery: Metformin should be discontinued 48 hours before elective surgery with general spinal or peridural anaesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition provided normal renal function has been established.
Other precautions: All patients should continue their diet with a regular distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.
The usual laboratory tests for diabetes monitoring should be performed regularly.
Metformin alone never causes hypoglycaemia, although caution is advised when it is used in combination with insulin or other oral antidiabetics (e.g. sulfonylureas or meglitinides).
The tablet shells may be present in the faeces. Patients should be advised that this is normal.
