Do glucagon‑like peptide‑1 (GLP‑1) receptor agonists cause clinically significant changes in thyroid hormone levels or increase the risk of thyroid dysfunction?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 16, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Do GLP-1 Receptor Agonists Cause Clinically Significant Changes in Thyroid Hormone Levels?

GLP-1 receptor agonists do not cause clinically significant changes in thyroid hormone levels (TSH, T3, T4) in the vast majority of patients, but they carry a black-box warning for medullary thyroid carcinoma risk based on rodent data and are absolutely contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN 2). 1, 2

Thyroid Hormone Level Effects

Evidence from Clinical Practice

  • One isolated case report documented suppressed TSH levels in a post-thyroidectomy patient on stable levothyroxine who started semaglutide, requiring a 25% levothyroxine dose reduction. 3 This represents the only published evidence of direct thyroid hormone alterations.

  • The proposed mechanisms for this single case include: direct GLP-1 receptor effects on TSH secretion, altered levothyroxine absorption from delayed gastric emptying, or weight-loss-related changes in levothyroxine requirements. 3

  • This is an extremely rare occurrence and does not represent a pattern seen in clinical trials or widespread clinical use. The case highlights that patients on narrow-therapeutic-index medications like levothyroxine may warrant closer monitoring during GLP-1 RA initiation and titration. 3

GLP-1 Receptors in Thyroid Tissue

  • GLP-1 receptors are expressed in multiple organs including the thyroid gland, which explains some pleiotropic effects of these medications. 4, 5

  • In human thyroid tissue, GLP-1 receptor expression has been documented in:

    • Medullary thyroid carcinoma and C-cell hyperplasia (consistently present) 6
    • Papillary thyroid carcinoma (18% of cases) 6
    • Normal C-cells (approximately 35% of C-cells in 33% of control thyroid specimens) 6

  • Despite this receptor expression, no clinical trials have demonstrated that GLP-1 RAs alter thyroid hormone production or secretion in humans. 7

Thyroid Cancer Risk: The Real Concern

Medullary Thyroid Carcinoma (MTC)

  • In rodents, GLP-1 receptor agonists cause dose-related and treatment-duration-dependent increases in thyroid C-cell tumors (adenomas and carcinomas). 1

  • In humans, the relevance of rodent C-cell tumor data remains uncertain. One case of MTC was reported in a patient treated with dulaglutide who had pretreatment calcitonin levels approximately 8 times the upper limit of normal. 1

  • Randomized controlled trials show thyroid cancer as a rare event with imprecise effect estimates but without conclusive evidence of increased risk. 7

  • Observational studies yield inconsistent results with low event rates for thyroid cancer. 7

  • Pharmacovigilance data from the European database (EudraVigilance) showed disproportionate reporting of thyroid cancer with GLP-1 RAs, particularly medullary thyroid cancer (PRR 221.5,95% CI 155.7-315.1) and general thyroid neoplasm (PRR 35.5,95% CI 25.9-48.5). 8 However, these reports do not establish causality.

Non-Medullary Thyroid Cancer

  • GLP-1 receptors are expressed in 18% of papillary thyroid carcinomas, but the clinical impact of GLP-1 RAs on papillary thyroid cancer growth or development is unknown. 6, 9

  • The biological plausibility for non-MTC risk in humans is less clear than for MTC. 7

Clinical Recommendations

Absolute Contraindications

  • Personal or family history of medullary thyroid carcinoma 1, 2
  • Multiple endocrine neoplasia syndrome type 2 (MEN 2) 1, 2

Monitoring Guidance

  • Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early MTC detection in patients treated with GLP-1 RAs and may increase unnecessary procedures due to low test specificity and high background thyroid disease incidence. 1

  • If serum calcitonin is measured and significantly elevated (usually >50 ng/L in MTC patients), further evaluation is warranted. 1

  • Patients with thyroid nodules on physical examination or imaging should be evaluated regardless of GLP-1 RA use. 1

  • For patients on levothyroxine or other narrow-therapeutic-index medications, consider more frequent monitoring during GLP-1 RA initiation and titration, though this is based on a single case report rather than systematic evidence. 3

Patient Counseling

  • Inform patients about symptoms of thyroid tumors: neck mass, dysphagia, dyspnea, or persistent hoarseness. 1

  • Reassure patients that evidence from randomized controlled trials indicates thyroid cancer occurrence is infrequent in individuals exposed to GLP-1 RAs, and there is no conclusive evidence of elevated thyroid cancer risk in humans. 7

Common Pitfalls

  • Do not withhold GLP-1 RAs from eligible patients due to unproven thyroid cancer concerns – the substantial cardiovascular, renal, and metabolic benefits outweigh theoretical risks in patients without contraindications. 7

  • Do not perform routine calcitonin screening in asymptomatic patients starting GLP-1 RAs – this increases false positives and unnecessary interventions. 1

  • Do not confuse the rodent C-cell tumor data with human risk – the human relevance has not been established despite decades of clinical use. 1, 7

  • Do not assume all patients on levothyroxine will require dose adjustments – the single case report represents an isolated occurrence, not a class effect. 3

References

2
Guideline

Pharmacological Management of Obesity

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

4
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

5
Guideline

Semaglutide Mechanism and Efficacy in Insulin Resistance

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

6
Research

Glucagon like peptide-1 receptor expression in the human thyroid gland.

The Journal of clinical endocrinology and metabolism, 2012

7
Research

Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review.

Thyroid : official journal of the American Thyroid Association, 2024

Related Questions

Is GLP-1 (Glucagon-like peptide-1) receptor agonist safe in patients with hyperthyroidism?
What are the contraindications of Wegovy (semaglutide) in patients with thyroid cancer?
Can GLP‑1 receptor agonists (e.g., exenatide, liraglutide, semaglutide, dulaglutide) cause alterations in thyroid function or increase the risk of thyroid disease?
Is it safe to give tirzepatide (glucagon-like peptide-1 receptor agonist) to a patient with a history of hypothyroidism and papillary thyroid carcinoma?
How to evaluate and manage a patient with a history of thyroidectomy, claiming severe metabolic and endocrine damage, and responding to treatment with GLP-1 (Glucagon-like peptide-1) analogs and low-dose naltrexone?
An elderly cachectic patient with chronic obstructive pulmonary disease and bronchiectasis who has a new pseudomonal pneumonia and recent thoracentesis now has an elevated International Normalized Ratio, low fibrinogen, undetectable haptoglobin, a negative Coombs test, and chronic thrombocytopenia of 66 ×10⁹/L; what is the most likely diagnosis and appropriate initial management?
Can I give Bactrim (trimethoprim‑sulfamethoxazole) to a patient with an estimated glomerular filtration rate of 38 mL/min/1.73 m²?
Is a non‑contrast CT or a contrast‑enhanced CT better for visualizing pulmonary nodules?
What is the most likely diagnosis and recommended work‑up and treatment for a patient with hemoglobin 9.5 g/dL, hematocrit 31.8 %, mean corpuscular volume 78.1 fL, mean corpuscular hemoglobin 23.3 pg, mean corpuscular hemoglobin concentration 29.9 g/dL, and red‑cell distribution width 15.8 %?
What is the recommended empiric oral therapy for an acute urinary tract infection in a 59‑year‑old man, considering sulfonamide allergy, recent fluoroquinolone use, renal impairment, and the need for a urine culture?
I am a healthy adult with a painless subconjunctival hemorrhage, no recent eye trauma, vision changes, pain, discharge, or systemic bleeding problems; how should it be managed and when should I follow up?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question