Toxicology of oral antidiabetic medications

Purpose. The toxicology of oral antidiabetic agents is reviewed. Summary. Type 2 diabetes mellitus is increasing to near epidemic proportions, with a reported 190 million patients worldwide. Use of oral antidiabetic medications is increasing along with a proportional increase in adverse events. Oral antidiabetic medications can be separated by mechanism of action into two groups: hypoglycemics (sulfonylureas and meglitinides) and antihyperglycemics (biguanides and alpha-glucosidase inhibitors). The hypoglycemic agents pose a significant risk of morbidity, mortality, and permanent sequelae secondary to prolonged periods of hypoglycemia. However, outcomes are routinely good if intervention is initiated early, with the primary goal return of euglycemia using supplemental dextrose infusion and octreotide to reduce further insulin secretion. Metformin-associated lactic acidosis (MALA) can occur with both acute and chronic metformin exposure. While MALA is not common, its associated rates of morbidity and mortality can be high. Secondary to MALA, the patient may experience changes in the central nervous system, cardiovascular collapse, renal failure, and death. The primary goals of therapy are restoration of acid-base status and removal of metformin, using hemodialysis and bicarbonate therapy. There is no specific antidote for MALA. The alpha-glucosidase inhibitors and thiazolidinediones pose minimal risk of adverse events in acute overdose. However, acarbose and all thiazolidinediones have been reported to produce hepatic injury with chronic therapy. Cessation of therapy with the offending agent and supportive care are the mainstays of overdose management with these drugs. Conclusion. The toxicity of oral antidiabetic agents differs widely in clinical manifestations, severity, and treatment.