Metformin-induced lactic acidosis in the presence of acute renal failure

Abstract

Lactic acidosis occourred in 6 metformintreated diabetic patients. Five of them had received 1.6 to 2.4 g metformin per day over a period of weeks or years. Acute renal failure, induced by i. v. pyelography, arteriography, or severe dehydration, preceded lactic acidosis by a few days and apparently precipitated it. The sixth patient had normal renal function prior to taking a massive overdose of metformin in an attempt at suicide. The metabolic pattern was very similar to that observed in phenformin-induced lactic acidosis: severe metabolic acidosis (pH: 7.02 + 0.95; HCO~: 6.3 + 0.9 mmol/l; PaCO2:25 _+ 4mmHg; PaO2:110 + 19 mmHg); hyperlactataemia (18.4 + 3.3 retool/l) and high lactate/pyruvate ratio (51 _+ 5); high blood alanine (2.82 + 1.10 mmol/1); high 3-hydroxybutyrate (15.8 + 3.3 mmol/1) and high 3-hydroxybutyrate/ acetoacetate ratio (26 + 10). Hypoglycaemia (25 to 60 mg per 100 ml) was observed in 4 patients, in spite of high glucagon (760 _+ 148 pg/ml) and low insulin (13 + 5 ~tU/ml) levels. A guanidine substance was characterized in the plasma at concentrations 45 to 110 ~tg/ml; it was similar to metformin and distinct from creatinine, according to chromatographic and other criteria; its concentration in the plasma decreased during dialysis, and the same substance appeared in the dialysis effluent. The treatment included massive alkalinization (710 ___ 130 mmol/1 i. v. for 48 h), plasma volume expanders (5630 + 1000 ml/48 h), forced-diuresis and/or dialysis, insulin (30 +_ 10 U/48 h) and glucose (300 _+ 50 g/48 h). -It is concluded that: 1. metformin, like other biguanides, can induce lactic acidosis; 2. acute renal failure is a prominent causal factor; 3. pharmacokinetics of metformin account for this fact since metformin cannot be inactivated by the liver (as distinct from phenformin) and is normally excreted by the kidney; 4. accumulation of biguanide is suggested by guanidine assay in the plasma; 5. metformin should not be prescribed in the presence of renal failure.

Non Insulin-Dependent Diabetes Mellitus (Type 2) Secondary Failure. Metformin-Glibenclamide Treatment

“…In 330 patients with lactic acidosis, half of which died, 71 % were also affected by other diseases: 64% by heart diseases, 51 % by renal failure, 28% by infection, 25% by pulmonary disorders and 28 % by hepatic diseases as demostrated by Luft et al (17). In this study only 4% of patients were treated with Metformin in contrast with 86% treated with Phenformin and 10% treated with Buformin (57)(58)(59)(60)(61) (13 years) old subject". Glibenclamide represents the first secondgeneration sulphonylurea.…”

Lactic acidosis in biguanide-treated diabetics

“…The share in the reported cases of lactic acidosis (n = 31) are: buformin 84%, metformin 3%, and phenformin 13%. Furthermore metformin induced lactic acidosis seems to occur only with marked renal impairment [25]. The lowest serum creatinine concentration observed in our collected metformin cases was 3.0mg/100ml, whereas during phenformin therapy lactic acidosis was observed with normal -or approximately normal -creatinine concentrations (Table 4).…”

The effect of short-term administration of antidiabetic biguanide derivatives on the blood lactate levels in healthy subjects

“…It has been claimed also that treatment of diabetics with other biguanide derivatives -buformin and metforrain -causes no such complication [8,9]. Although development of lactic acidosis has been reported recently during treatment with buformin [10,11] and metformin [12,13], the number of such cases so far published is much lower.…”