Metformin-associated lactic acidosis: risk factors and prognostic factors

Abstract

Introduction Metformin, an oral hypoglycemic drug, belongs to thebiguanide class and is now generally accepted as first-line treatmentin type 2 diabetes mellitus, especially in overweight patients [1].In some predisposing conditions, the use of metformin may resultin metformin-associated lactic acidosis (MALA), a rare adverse eventassociated with a high mortality rate [2]. The aim of this studyis to assess risk factors and prognostic factors in patients withMALA. Methods We conducted a retrospective study of patients withMALA admitted to the ICU of ASL 2 Chieti between 1 January 2008 and30 September 2012. The eligibility criteria were: diagnosis of diabetesmellitus type 2, treatment with oral hypoglycemic drugs containingmetformin, increased anion gap metabolic acidosis (pH <7.35, HCO3-<22 mmol/l, lactate >5 mmol/l). For each patient we evaluated: sex,age, home care, SAPS II score [3], blood tests. Results Ten patientswere selected, f ve males and f ve females, with a mean age of 72.2.On admission, nine of 10 patients had a framework of general illnessand acute renal failure; one patient appeared with a probable acuteabdomen not subsequently confirmed on CT. Eight patients had a stateof dehydration resulting from gastroenteritis, diarrhea, fever; twopatients had taken NSAIDs in the days prior to hospitalization. Nopatient, in these conditions, has discontinued treatment with metformin.All patients showed a critical clinical framework with a SAPS IImean score of 77.5. Cardiovascular and respiratory support was requiredin all cases. The hemogas analysis showed that patients had a severemetabolic acidosis (mean pH = 6.96) with increased plasma lactate(mean lactate = 15.93 mmol/l). Prothrombin activity was normal ineight of 10 patients. The overall mortality was 70%. Conclusion Patienteducation on correct use of metformin is essential to prevent MALA,specially in those clinical conditions of increased risk (for example,acute renal failure), as recommended by the AIFA 2011 guidelines[4]. In our study, a higher plasma concentration of lactate representsthe main negative prognostic factor, as pointed out by other studies[5]. The prothrombin activity, which is considered to be a decisiveprognostic factor in the study of Peters and colleagues [6], wasnot impaired in patients with poor outcome.