Mounjaro (tirzepatide) is a medication approved for type 2 diabetes, used alongside diet and exercise. It functions as a dual agonist, activating both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Beyond blood sugar control, Mounjaro also aids in weight management. Its potential link to cancer is a common concern that warrants a closer look at the scientific evidence.
Origin of the Cancer Concern
Concerns about a potential link between Mounjaro and cancer, particularly thyroid cancer, stem from early animal studies. These preclinical investigations in rodents revealed an increased incidence of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in rats and mice exposed to GLP-1 receptor agonists and dual GLP-1/GIP agonists. These tumors were observed after long-term exposure to doses sometimes higher than those used in humans.
The mechanism behind these rodent findings involves stimulating thyroid C-cells, which produce calcitonin. GLP-1 receptor agonists activate these C-cells, leading to C-cell hyperplasia (an increase in cell number) and tumor formation. This effect is mediated through GLP-1 receptors on rodent C-cells.
Significant physiological differences exist between rodents and humans concerning thyroid C-cells. Rodents possess a higher density of GLP-1 receptors on their thyroid C-cells compared to humans. Human thyroid C-cells express very few or no GLP-1 receptors, and studies in non-human primates have not shown similar C-cell activation or hyperplasia. This species-specific difference suggests that rodent study findings may not directly translate to humans.
Clinical Trial Findings
Large-scale human clinical trials for Mounjaro provide important insights into its safety profile. These trials, involving thousands of participants with type 2 diabetes, have not demonstrated an increased risk of thyroid C-cell tumors or other cancers in individuals treated with Mounjaro. A comprehensive analysis of Mounjaro clinical trials (spanning 26 to 72 weeks) found cancer rates in the Mounjaro group similar to control groups. No cases of medullary thyroid carcinoma (MTC) were observed during these trials.
Clinical trials offer valuable information, but have inherent limitations. Their duration, typically several months to a few years, may not be long enough to detect rare cancers that develop slowly. Additionally, trial populations are specific and may not fully represent the broader patient population.
Despite these limitations, the current human evidence is reassuring. Post-market surveillance, which monitors a drug’s safety after public availability, continues to gather long-term data. Some real-world data analyses suggest GLP-1 receptor agonists may reduce the risk of certain obesity-related cancers, aligning with the understanding that weight loss can lower cancer risk.
Regulatory Warnings and Patient Considerations
Regulatory bodies, such as the U.S. Food and Drug Administration (FDA), have issued warnings regarding Mounjaro. Mounjaro carries a “boxed warning,” the most serious type of warning issued by the FDA. This warning highlights the potential risk of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), observed in rodent studies. It emphasizes that it is currently unknown whether Mounjaro causes these tumors in humans.
Given animal study findings and MTC’s serious nature, Mounjaro is contraindicated for individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). MEN 2 is a rare genetic condition that increases the risk of developing MTC and other endocrine tumors. These contraindications prioritize patient safety, even though a direct link in humans has not been established.
Patients using Mounjaro should be aware of potential thyroid tumor symptoms. These include a lump or swelling in the neck, persistent hoarseness, difficulty swallowing, or shortness of breath. If any symptoms develop, promptly discuss them with a healthcare provider. Patients should also communicate their full medical history, including any family history of thyroid cancer or MEN 2, with their healthcare team before or during Mounjaro treatment.