Can a higher dose of Monjario (medication to lower blood sugar levels) cause hypoglycemia in patients with diabetes?

Can Higher Doses of Monjaro Cause Hypoglycemia?

Monjaro (tirzepatide) alone does not cause clinically significant hypoglycemia, even at higher doses, but the risk increases substantially when combined with insulin or insulin secretagogues like sulfonylureas. 1

Hypoglycemia Risk Profile of Monjaro Monotherapy

• As monotherapy, Monjaro has minimal hypoglycemia risk across all dose levels (5 mg, 10 mg, and 15 mg), with blood glucose <54 mg/dL occurring in 0% of patients at all doses in a 40-week trial. 1
• No severe hypoglycemia events occurred with Monjaro monotherapy at any dose level. 1
• This low hypoglycemia risk is characteristic of GLP-1 receptor agonists and incretin mimetics, which cause glucose-sensitive insulin secretion rather than continuous insulin stimulation. 2, 3

Hypoglycemia Risk When Combined With Other Medications

The hypoglycemia risk with Monjaro is dose-dependent when combined with high-risk medications:

When Added to Basal Insulin (with or without Metformin)

• Blood glucose <54 mg/dL occurred in 13% with placebo, 16% with 5 mg, 19% with 10 mg, and 14% with 15 mg Monjaro over 40 weeks. 1
• Severe hypoglycemia occurred in 0% with placebo, 0% with 5 mg, 2% with 10 mg, and 1% with 15 mg. 1
• This demonstrates that higher doses (particularly 10 mg) carry increased hypoglycemia risk when combined with insulin. 1

When Combined With Sulfonylureas

• Over 104 weeks of treatment, hypoglycemia (glucose <54 mg/dL) occurred in 13.8% with 5 mg, 9.9% with 10 mg, and 12.8% with 15 mg Monjaro. 1
• Severe hypoglycemia occurred in 0.5% with 5 mg, 0% with 10 mg, and 0.6% with 15 mg. 1
• Guidelines specifically warn that incretin mimetics like Monjaro may cause hypoglycemia when taken with insulin secretagogues or insulin. 2

Clinical Management Recommendations

When initiating or escalating Monjaro doses:

• Reduce or discontinue insulin secretagogues (sulfonylureas, meglitinides) or decrease insulin doses when starting Monjaro or increasing to higher doses to prevent hypoglycemia. 2
• Patients on insulin or sulfonylureas should be educated on hypoglycemia signs and symptoms and carry a source of quick-acting carbohydrates (15-20 g glucose). 2, 4
• Consider switching from sulfonylureas to Monjaro rather than adding Monjaro to sulfonylureas, as this reduces hypoglycemia risk while maintaining glycemic control. 2

For patients with HbA1c substantially below target (<6.5%):

• De-intensify medications with hypoglycemia risk (insulin, sulfonylureas) when adding or escalating Monjaro doses. 2, 5
• The American College of Physicians recommends de-intensifying therapy when HbA1c is below 6.5% to avoid hypoglycemia. 5

Important Caveats

• Metformin can be safely continued with any dose of Monjaro as it does not cause hypoglycemia when used alone. 2, 5
• Patients with chronic kidney disease (CKD stages 3-5) have increased hypoglycemia risk due to decreased insulin clearance and impaired renal gluconeogenesis, requiring closer monitoring when combining Monjaro with insulin or sulfonylureas. 2
• The dose-response relationship for hypoglycemia with Monjaro is not linear—the 10 mg dose showed the highest severe hypoglycemia rate (2%) when combined with insulin, compared to 1% with 15 mg. 1
• Continuous glucose monitoring should be considered for patients at high risk for hypoglycemia when using Monjaro with insulin or sulfonylureas. 2, 4