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High Yield Facts

  • Oral anti-diabetic drugs function by either increasing insulin secretion or by modulating blood glucose concentrations through a variety of mechanisms other than the increase of blood insulin concentration.

  • Significant poisoning is associated with sulfonylureas and metformin only.

  • Sulfonylurea overdose can produce life-threatening hypoglycemia, and the antidote of choice is octreotide.

  • It is inadvisable to administer prophylactic intravenous dextrose to normoglycemic children with sulfonylurea ingestion because this may mask and prolong the appearance of sulfonylurea-induced hypoglycemia.

  • Asymptomatic, euglycemic young children presenting with a history of sulfonylurea ingestion require 8 hours of observation and no prophylactic intravenous dextrose therapy.

  • Metformin overdose can result in life-threatening lactic acidosis that may require hemodialysis.

There are 18.8 million people in the United States diagnosed with Type II diabetes (T2DM).1 The mainstay of T2DM treatment is oral anti-diabetic therapy, and pediatric exposures may result from the significant number of homes with these medications. However, not all oral anti-diabetic agents produce hypoglycemia in overdose. Biguanides, thiazolidinediones, and alpha-glucosidase inhibitors help to maintain euglycemia in the body but do not cause hypoglycemia. Sulfonylureas, meglitinides, and to a lesser extent dipeptidyl peptidase (DPP)-IV inhibitors increase pancreatic insulin and may cause hypoglycemia following overdose. Although a single sulfonylurea tablet may produce symptomatic hypoglycemia in a toddler, noteworthy sequelae have not been reported. Larger overdoses are associated with significant morbidity and mortality in older children and adults.2 Many oral anti-diabetic agents are prescribed in combination forms or in extended release forms. History should include careful questioning to determine all active ingredients in the product as well as release form. Both biguanides and thiazolidinediones may be prescribed in adolescents for treatment of diabetes. Chronic toxicity seen with these agents includes lactic acidosis (biguanides) and hepatotoxicity (thiazolidinediones). A summary of the expected toxicity from each class of oral anti-diabetic drugs is found in Table 121-1.

TABLE 121-1Oral Anti-Diabetic Drugs

Insulin Secretagogues



Sulfonylureas stimulate pancreatic beta cells to release insulin.3 (Figure 121-1). Second-generation sulfonylureas (glimepiride, glipizide, and glyburide) are more commonly prescribed than the first generation (tolbutamide and chlorpromide). All of the second-generation agents are rapidly absorbed, have a duration of action of approximately 24 hours, and a single dose may produce mild symptomatic hypoglycemia in a young child.

FIGURE 121-1

Site of action for insulin secretagogues. (Reproduced with permission from Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. ...

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