Short-term effect of tirzepatide on serum calcitonin in adults with obesity

PURPOSE: To evaluate whether short-term treatment with tirzepatide, a dual GIP/GLP-1 receptor agonist, is associated with measurable changes in serum calcitonin levels in adults with obesity and no known thyroid disease. METHODS: In this prospective observational study, 58 adults (mean age 47.5 ± 10.7 years; 72% female; mean BMI 41.4 ± 8.1 kg/m²) initiated tirzepatide therapy for weight loss. Serum calcitonin concentrations were measured at baseline and after 12 weeks of treatment. Secondary parameters included HbA1c and estimated glomerular filtration rate (eGFR). RESULTS: Mean baseline calcitonin was 2.7 ± 3.0 pg/mL, increasing to 3.2 ± 3.7 pg/mL post-treatment. This change was statistically significant (Wilcoxon Z = − 3.0, p = 0.003) with a moderate effect size (r = 0.4), despite a small absolute increase. No participant exceeded the clinical calcitonin threshold of 20 pg/mL. No thyroid nodules were detected on ultrasound. CONCLUSION: Tirzepatide treatment over 12 weeks was associated with a modest but statistically significant increase in serum calcitonin levels in adults with obesity. However, absolute values remained within the normal range, and no clinically relevant thyroid abnormalities were observed. These findings support the short-term safety of tirzepatide in appropriately selected patients without known thyroid disease or risk factors for medullary thyroid carcinoma.