Pancreatitis and metformin: case-report and review of literature

Metformin is the most used anti-hyperglycemic agent for the treatment of Type 2 Diabetes Mellitus. It is considered a very good drug, with low risk and high benefit. Metformin intoxication can be due to massive ingestion or to a progressive accumulation due to renal failure. Fatal cases due to metformin intoxication have been described. With regard to that we present a fatal case of a fifty-six-year-old patient with severe metformin intoxication (100 μg/ml) who presented kidney failure, lactic acidosis, hyperglycemia and pancreatitis. He received alkalinization and hemodialysis therapy, afterwards which shortly hereby improved his condition, but the patient deceased after 7 days for a nosocomial pneumonia. Pancreatitis was confirmed by the post-mortem histopathological analysis. Acute pancreatitis as side effect of metformin is very rare, either in overdose or therapeutic dosage, and it has been attributed to an intrinsic toxicity mechanism. With regard to that, we performed a review of the literature of all cases in which pancreatitis was referred to metformin use in order to evaluate if this complication usually develops in presence of specific predisposing factors, or if it is unpredictable. From our review, according to the literature, we confirm that acute pancreatitis represents a very rare side effect of metformin, either in therapeutic dosage or overdose. In metformin intoxication, polypharmacy and high doses might be possible risk factors in order to develop pancreatitis. There is not a specific association of metformin related pancreatitis and hyperglycemia, even if pancreatitis is generally linked to glucose homeostasis alterations. It is possible to assume that the presence of hyperglycemia depends on the extent of pancreatitis that if much extended could lead to a deficit of insulin release and to an increase of blood glucose levels.