Can Wegovy (semaglutide) cause hypoglycemia?

Wegovy (Semaglutide) and Hypoglycemia Risk

When used alone, Wegovy (semaglutide) has minimal risk of hypoglycemia because it works in a glucose-dependent manner, but it may increase hypoglycemia risk when combined with insulin or insulin secretagogues.

Mechanism of Action and Hypoglycemia Risk

• Semaglutide (Wegovy) is a GLP-1 receptor agonist that stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner 1
• This glucose-dependent mechanism means that when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited, but this effect diminishes as blood glucose normalizes 1
• During induced hypoglycemia, semaglutide does not alter the counter-regulatory responses of increased glucagon compared to placebo 1
• GLP-1 receptor agonists, including semaglutide, have minimal risk for hypoglycemia when used as monotherapy 2

Risk Factors for Hypoglycemia with Wegovy

• Combination therapy risk: GLP-1 receptor agonists may increase the hypoglycemic potential of insulin and sulfonylureas when combined with those medications 2
• Specific guidance for patients taking incretin mimetics (GLP-1) with insulin secretagogues or insulin notes they may experience hypoglycemia 2
• For individuals taking GLP-1 receptor agonists with insulin secretagogues, recommendations include:
  • Consuming moderate amounts of carbohydrates at meals and snacks 2
  • Not skipping meals 2
  • Carrying a source of carbohydrates to reduce hypoglycemia risk during physical activity 2

Clinical Evidence on Hypoglycemia Risk

• In clinical trials, all GLP-1 receptor agonists demonstrated minimal risk for hypoglycemia when used alone 2
• A meta-analysis of semaglutide studies showed that semaglutide 2.4mg had a higher incidence of hypoglycemic events compared to liraglutide 3.0mg, semaglutide 1.0mg, and liraglutide 1.8mg 3
• However, the absolute risk of hypoglycemia with semaglutide monotherapy remains low due to its glucose-dependent mechanism of action 2

Special Populations and Considerations

• No dose adjustment of semaglutide is recommended for patients with renal impairment, including end-stage renal disease 1
• No dose adjustment is recommended for patients with hepatic impairment 1
• For elderly patients (≥65 years), no overall differences in safety were detected compared to younger patients, though greater sensitivity in some older individuals cannot be ruled out 1

Management of Hypoglycemia Risk

• When prescribing Wegovy with medications that increase hypoglycemia risk (insulin or sulfonylureas):
  • Consider lower doses of the insulin or insulin secretagogue 2
  • Educate patients on recognizing and managing hypoglycemia symptoms 2
  • Advise patients to monitor blood glucose more frequently, especially when initiating therapy 2
• For patients experiencing hypoglycemia while on combination therapy, treatment recommendations include using glucose tablets or carbohydrate-containing foods or beverages 2

Conclusion

Wegovy (semaglutide) alone has a low risk of causing hypoglycemia due to its glucose-dependent mechanism of action. The primary concern for hypoglycemia arises when Wegovy is combined with insulin or insulin secretagogues, which requires appropriate dose adjustments of these medications and patient education on hypoglycemia management.