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

There's more to see -- the rest of this topic is available only to subscribers.