AACE Endocrinology and Diabetes · Apr 18, 2026

Increased Levothyroxine Requirement After Tirzepatide Initiation

By Koç D, Vural Keskinler M

INTRODUCTION: Dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists such as tirzepatide are increasingly used for obesity management. These agents delay gastric emptying and may influence the absorption of orally administered drugs, including levothyroxine. CASE DESCRIPTION: A 48-year-old woman with class I obesity (BMI 32 kg/m²) was diagnosed with overt primary hypothyroidism (TSH 17.1 mIU/L; free T4 0.76 ng/dL). Levothyroxine 25 μg/d achieved biochemical normalization. Tirzepatide 2.5 mg weekly was initiated for weight management. Over 3 months, body weight decreased from 116 kg to 100 kg (-13.8%). Despite confirmed adherence and absence of interacting medications, TSH increased to 20.7 mIU/L with low-normal free T4. Levothyroxine dose was increased to 50 μg/d, resulting in TSH suppression (0.33 mIU/L). DISCUSSION: Weight loss is typically associated with reduced levothyroxine requirements; however, this case demonstrated the opposite pattern. Tirzepatide-induced delay in gastric emptying may have impaired levothyroxine absorption. Previous reports with glucagon-like peptide-1 receptor agonists have mainly described reduced levothyroxine requirements, suggesting that this interaction may be variable and patient-specific. CONCLUSION: Levothyroxine requirements may increase in some patients following tirzepatide initiation. Clinicians should consider reassessing thyroid function within 6-8 weeks after starting dual incretin therapy.

doi.org/10.1016/j.aed.2026.04.007 Open access PubMed 42978782 Interventions