Hypoglycemic Agent Poisoning

Basics

Description

  • Oral or parenteral agents that may cause hypoglycemia or other metabolic imbalances
  • Hypoglycemic poisoning may be intentional or unintentional (accidental)

Etiology

  • Insulin:
    • Enhances glucose uptake into cells
    • Limits glucose availability to the brain (most sensitive to hypoglycemia)
    • Influences potassium redistribution (hypokalemia)
  • Sulfonylurea and meglitinide agents:
    • Enhance insulin release from pancreatic β cells, reduce hepatic glucose production, and increase peripheral insulin sensitivity
    • Hypoglycemic effect enhanced by:
      • Polypharmacy (drug interactions)
      • Alcohol use and hepatic dysfunction (poor nutritional stores)
      • Renal insufficiency (decreased clearance)
  • GLP1 modulators:
    • Exenatide is an analog of glucagon-like peptide 1 (GLP1)
    • Gliptins (sitagliptin, saxagliptin, and linagliptin) inhibit DDP4 which normally inactivates GLP1
    • Net effects: Enhanced insulin secretion, delayed gastric emptying, and increased satiety
    • Unclear effects on glucose metabolism in overdose (data are lacking at this time)
  • Biguanide agents (metformin):
    • Antihyperglycemic agents:
      • Decrease elevated serum glucose concentrations
      • Generally do not cause hypoglycemia in isolation
    • In the presence of insulin, biguanides do the following:
      • Increase glucose uptake into cells
      • Limit glucose availability to the brain (most sensitive to hypoglycemia)
      • Influence potassium redistribution (hypokalemia)
      • Decrease GI glucose absorption
      • Decrease hepatic gluconeogenesis
      • Metabolize glucose to lactate in intestinal cells, which may accumulate and lead to profound lactic acidosis
  • Sodium glucose cotransporter-2 inhibitors:
    • Canagliflozin, empagliflozin
    • Interfere with renal reuptake of filtered glucose
    • Cause osmotic diuresis, but typically euglycemic when used as monotherapy:
      • Can potentiate effects of insulin/sulfonylureas
      • Can result in significant hypoglycemia in combination
      • Reported to cause Euglycemic DKA
  • Thiazolidinediones:
    • In the presence of insulin, thiazolidinediones increase glucose uptake and use and decrease gluconeogenesis
  • α-glucosidase inhibitors:
    • Lower systemic glucose by decreasing GI absorption of carbohydrates

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