Search

Metformin is currently the cornerstone of treatment of Type-2 diabetes mellitus with obesity (DM2). Its most serious side effect is metabolic acidosis referred to as metformin-induced lactic acidosis (MILA). The aim of our paper was to provide an overview of patients with MILA treated in a hospital serving a catchment area of 90 000. Overall, 23 cases of MILA were identified over a period of 18 years (0.2 a year per 1000 patients). Most patients were shown to have developed a mixed disturbance of acid-base balance (with other acidifying but, also, alkalizing disorders). Blood pH was on average low (pH 7.13), with the lowest and highest values being 6.81 and 7.47, respectively. Significant hypocapnia was present (average pCO2, 2.80 kPa), Lactate levels were 10.10 mmol/l (max. 19.8 mmol/l). Levels of BE were on average lowered (-19.25 mmol/l) as were bicarbonate levels (10.10 mmol/l). Levels of AG were high: 36.55 mmol/l. Patients' partial pressure of oxygen was relatively high (pO2, 13.25 kPa). Patients were usually diagnosed to have pre-renal acute renal failure (ARF), whose causes were later fully corrected in most survivors. In 17 patients, we were able to track down their creatinine levels before the pre-renal ARF, which were significantly higher in two cases only. Levels of glycemia were on average higher (15.85 mmol/l), with hypoglycemia detected in only three cases. The first significant disturbance and, probably, also the cause of MILA development in our patients was gastrointestinal tract involvement. While common infection - or the effect of metformin itself - caused vomiting and diarrhea, subsequent hypovolemia resulted in pre-renal ARF, which in turn led to an increase in metformin levels up to toxic values. Development of kidney failure was often unexpected and fast. The prognosis of patients with MILA was rather grim, with death rates reaching 48%. Administration of bicarbonates failed to improve the clinical status of most patients. The prognosis was poor in ventilated patients, with a 75% death rate. Hypercapnia seems to be the underlying mechanism preventing the development of critical intracellular acidosis in MILA. The low respiratory volumes limiting hypocapnia appear to pose a risk in MILA patients. The most effective therapeutic option in our group of patient was elimination of metformin from the body (using hemodialysis or CVVHD). Limitation of aerobic metabolism is likely not only to be an undesirable but, also, the main therapeutic effect of metformin. Decreased energy income, ATP deficiency affect the underlying mechanisms determining basic mechanism of cells. The resultant effect is increased influx of glucose into the cell enabling ATP formation (via anaerobic glycolysis). This mechanism explains why metformin decreases production of glucose by liver cells and restores glucose consumption by muscle cells from blood, even if not responding adequately to insulin-stimulated impulses. The unique kinetics of metformin enables limited auto regulation. At present, metformin belongs to the safest medications of its class. Nevertheless - if we are forced to take medication that reduces the effect of unwanted chronic energy surplus in T2DM treatment, the risk of development of the MILA persists. [ABSTRACT FROM AUTHOR]