Can Mounjaro (tirzepatide) cause hypoglycemia?

Mounjaro (Tirzepatide) and Hypoglycemia Risk

Mounjaro (tirzepatide) can cause hypoglycemia, but primarily when used in combination with insulin or insulin secretagogues such as sulfonylureas, rather than when used alone.

Mechanism of Action and Hypoglycemia Risk

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Its mechanism affects blood glucose in several ways:

• Stimulates insulin secretion in a glucose-dependent manner
• Reduces glucagon secretion when glucose levels are elevated
• Slows gastric emptying
• Reduces appetite and food intake

Risk Assessment

The FDA label for Mounjaro specifically addresses hypoglycemia risk:

• When used alone: Minimal risk of clinically significant hypoglycemia 1
• When used with insulin secretagogues or insulin: Significantly increased risk of hypoglycemia, including severe hypoglycemia 1

Clinical Evidence of Hypoglycemia Risk

Clinical trials have demonstrated the following hypoglycemia rates with tirzepatide:

• In the SURPASS-2 trial comparing tirzepatide to semaglutide, hypoglycemia (blood glucose <54 mg/dL) was reported in only 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group) of patients on tirzepatide 2

• In the SURPASS-AP-Combo trial, tirzepatide was associated with low rates of hypoglycemia across different patient subgroups when not combined with insulin secretagogues 3

Risk Factors for Hypoglycemia with Mounjaro

The risk of hypoglycemia is significantly higher in certain scenarios:

1. Concomitant medications:

   • Combination with sulfonylureas 1
   • Combination with insulin 1
   • Combination with other insulin secretagogues 1

2. Patient factors:

   • Advanced age (≥65 years) 4
   • Renal impairment 1
   • History of hypoglycemia 4

Management Recommendations

For Prescribers

1. When initiating Mounjaro with insulin secretagogues or insulin:

   • Consider reducing the dose of sulfonylurea or insulin to minimize hypoglycemia risk 1
   • Monitor blood glucose more frequently during dose titration 1

2. Patient education:

   • Educate patients about signs and symptoms of hypoglycemia 1
   • Provide guidance on how to treat hypoglycemia (15-20g fast-acting carbohydrate) 5

For Patients Taking Mounjaro

1. Monitoring:

   • Check blood glucose more frequently when starting or increasing Mounjaro dose, especially if on insulin or sulfonylureas
   • Be particularly vigilant during periods of increased physical activity or reduced food intake

2. Hypoglycemia prevention:

   • Maintain consistent meal timing and carbohydrate content 5
   • Avoid skipping meals 5
   • Consider a bedtime snack containing complex carbohydrates if at risk 5
   • Limit alcohol consumption, which can increase hypoglycemia risk 5

Special Considerations

• Elderly patients: More susceptible to hypoglycemia; consider more conservative dosing of concomitant medications 4

• Renal impairment: Mounjaro has been associated with gastrointestinal adverse reactions that may lead to dehydration and potentially acute kidney injury; monitor renal function when initiating or escalating doses 1

• Surgical procedures: Mounjaro may cause delayed gastric emptying which can affect anesthesia; inform healthcare providers about Mounjaro use before planned procedures 1

Bottom Line

While Mounjaro alone carries minimal risk of hypoglycemia due to its glucose-dependent mechanism of action, the risk increases substantially when combined with insulin or insulin secretagogues. Appropriate dose adjustments of these concomitant medications, patient education, and vigilant monitoring are essential to minimize hypoglycemia risk.