Metformin and antihypertensive therapy with drugs blocking the renin angiotensin system, a cause of concern?

Background: The burden of diabetes mellitus type 2 (DM2) is increasing worldwide. The combination of DM2 and hypertension (HT) is frequently encountered. Concurrent use of drugs blocking the renin angiotensin system (angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)) and metformin have become frequent in this group of patients. That combination can become life-threatening under certain circumstances. Method: We present 5 patients with DM2 and HT who developed severe metformin-associated lactic acidosis in a setting with acute renal failure, precipitated by dehydration and aggravated by the use of ACEI or ARB. Results: None of the patients had reduced renal function before the acute illness. They were admitted to the hospital in critical condition with severe metabolic acidosis (pH 6.60 -6.94), high S-lactate (14 - 23 mmol/l) and S-creatinine 796 - 1,621 μmol/l. They were all hypothermic and 3 were hypoglycemic. All developed circulatory and respiratory collapse. They were treated with either intermittent bicarbonate hemodialysis (HD) or with continuous venovenous hemodiafiltration (CWHDF) and bicarbonate buffering. All patients recovered without renal sequela. Conclusion: We believe that the incidence of metformin-associated lactic acidosis in Norway may become more frequent due to increased use of metfonnin and drugs blocking the renin angiotensin system. The awareness of lactic acidosis as a complication to the use of metformin in predisposed individuals is important. General advice should be given to patients regarding reduction of dosage or withdrawal of the drugs during acute inter-current illness with dehydration. Early diagnosis and treatment of metformin-associated lactic acidosis are crucial for the patient outcome. Hemodialysis can be life-saving and should be started without delay.