Can Mounjaro (tirzepatide) cause hypercalcemia?

Tirzepatide (Mounjaro) and Hypercalcemia

Based on current evidence, tirzepatide (Mounjaro) has not been associated with hypercalcemia as a known side effect. The most common adverse effects are gastrointestinal in nature, including nausea, vomiting, diarrhea, and constipation.

Mechanism of Action and Side Effect Profile

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works through multiple mechanisms to:

• Enhance weight loss effects
• Reduce appetite and food intake
• Slow gastric emptying
• Improve insulin sensitivity and glucose metabolism 1

The documented side effects of tirzepatide include:

• Gastrointestinal symptoms (nausea, diarrhea, vomiting, constipation) 2, 1
• Alopecia 2
• Abdominal pain 2

Calcium Metabolism and Tirzepatide

Unlike certain medications known to cause hypercalcemia, such as:

• Thiazide diuretics, which can cause severe hypercalcemia (reported cases with calcium levels as high as 19.8 mg/dL) 3
• Teriparatide (recombinant parathyroid hormone), which directly affects calcium metabolism 4, 5

Tirzepatide does not have a direct mechanism that would affect calcium metabolism or bone turnover in a way that would lead to hypercalcemia.

Monitoring Recommendations

While hypercalcemia is not a reported concern with tirzepatide, monitoring should focus on:

1. Blood glucose levels and HbA1c
2. Weight changes
3. Gastrointestinal symptoms
4. Renal function 1

Important Considerations for Patients with Hypercalcemia

If a patient on tirzepatide develops hypercalcemia, consider alternative causes:

• Primary hyperparathyroidism
• Malignancy
• Vitamin D toxicity
• Other medications (thiazides, lithium)
• Multiple myeloma (which can present with hypercalcemia) 2

Clinical Implications

For patients with pre-existing calcium disorders:

• No specific contraindications exist for using tirzepatide in patients with history of hypercalcemia
• Unlike denosumab, which has been associated with hypocalcemia 2, tirzepatide has not been linked to calcium disturbances

Conclusion

When evaluating a patient on tirzepatide with hypercalcemia, clinicians should investigate other potential causes rather than attributing it to the medication. The comprehensive safety profile established through the SURPASS clinical trials did not identify hypercalcemia as an adverse effect of tirzepatide 6, 7.