The large studies are reassuring. Across Scandinavian registries, a six-country cohort and a 48-trial meta-analysis, GLP-1 use was not associated with a clear rise in thyroid cancer, and the upper bound is a few extra cases per 10,000 treated. The boxed warning and the MTC/MEN2 contraindication remain on the label, and medullary carcinoma is too rare and too slow for current follow-up to settle.
Key points
- In France, 1 to 3 years of use was associated with thyroid cancer (aHR 1.58) and medullary carcinoma (aHR 1.78) [1].
- In Scandinavia, with 145,410 users, the HR was 0.93 (95% CI 0.66 to 1.31) [2]. A six-country study gave 0.81 [3].
- A 2026 meta-analysis of 48 trials: OR 1.37 (0.82 to 2.31), from 1 fewer to 9 more cases per 10,000 treated [5].
- The C-cell effect is clear in rodents and minimal in primates. The warning and the MTC/MEN2 contraindication remain [6][8].
US status (October 2026): Semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are FDA-approved. See the semaglutide and tirzepatide status pages.
The warning comes from rodent C-cells
In rodents, GLP-1 agonists activate thyroid C-cells, raise calcitonin and drive proliferation. Human and monkey C-cells express little GLP-1 receptor, and 20 months of liraglutide at more than 60 times human exposure was not associated with hyperplasia in monkeys [6]. In mice, the effect does not appear without the GLP-1 receptor and was not associated with RET activation [7]. Even so, the authors cautioned that long-term consequences in the human thyroid “remain unknown” [6].
That is why the tirzepatide label (revised August 2026) keeps the boxed warning: “In rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures.” It also keeps the contraindication in a history of medullary thyroid carcinoma (MTC) or MEN2 [8].
France produced the signal
In 2023 a case-control study in the French national database (2,562 cases, 45,184 controls) associated 1 to 3 years of GLP-1 use with all thyroid cancer (aHR 1.58; 95% CI 1.27 to 1.95) and medullary carcinoma (aHR 1.78; 1.04 to 3.05) [1]. The main criticism was detection bias. People prescribed a drug with a thyroid warning tend to get more ultrasounds and calcitonin tests.
The large studies did not reproduce it
| Study | Population | Result |
|---|---|---|
| Scandinavia, BMJ 2024 [2] | 145,410 GLP-1 users vs 291,667 DPP-4 inhibitor users | HR 0.93 (0.66 to 1.31). Incidence 1.33 vs 1.46 per 10,000 person-years. MTC: HR 1.19 (0.37 to 3.86) |
| Six countries, Thyroid 2025 [3] | 98,147 users | Pooled HR 0.81 (0.59 to 1.12). Median follow-up 1.8 to 3.0 years |
| Type 2 diabetes cohort, Diabetes Care 2025 [4] | 460,032 users, outcome thyroid tumors | HRs 0.78 to 1.03 vs SGLT2 inhibitors, DPP-4 inhibitors and sulfonylureas. None elevated |
| Meta-analysis, Ann Intern Med 2026 [5] | 48 trials, 94,245 participants | OR 1.37 (0.82 to 2.31). From 1 fewer to 9 more cases per 10,000 treated. Moderate certainty, consistent for semaglutide and tirzepatide |
The six-country authors called their follow-up “insufficient to rule out excess risk with long-term use” [3].
- 0.93: thyroid cancer HR in 145,410 Scandinavian users [2]
- Up to 9: extra cases per 10,000 treated (upper bound, 48 trials) [5]
- More than 60 times: exposure in monkeys without C-cell hyperplasia [6]
Medullary carcinoma cannot be ruled out yet
The 2024 to 2026 data are reassuring for thyroid cancer overall. The absolute risk, if any, is a few cases per 10,000 [2][5]. Medullary carcinoma is rare, its intervals are wide, and follow-up remains short for a slow-growing tumor [2][3]. The French signal is plausibly surveillance bias, but it has not been disproven [1].
What this means for your protocol
Screen for a personal or family history of MTC or MEN2 at intake. That contraindication remains on the label [8]. Routine monitoring with calcitonin or ultrasound is not established by these studies, and practice varies between centers. When a patient asks, give the numbers: no clear increase in the large studies, and an upper bound of a few cases per 10,000. For how prescribing oversight is structured, see weight management programs.
References
- Bezin J, et al. GLP-1 receptor agonists and the risk of thyroid cancer. Diabetes Care. 2023;46(2):384-390. PMID 36356111. Link
- Pasternak B, et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ. 2024;385:e078225. PMID 38683947. Link
- Baxter SM, et al. Glucagon-like peptide 1 receptor agonists and risk of thyroid cancer: an international multisite cohort study. Thyroid. 2025;35(1):69-78. PMID 39772758. Link
- Morales DR, et al. Risk of thyroid tumors with GLP-1 receptor agonists: a retrospective cohort study. Diabetes Care. 2025;48(8):1386-1394. PMID 40465422. Link
- Ko A, et al. Risk for cancer with glucagon-like peptide-1 receptor agonists and dual agonists: a systematic review and meta-analysis. Ann Intern Med. 2026;179(2):216-229. PMID 41359966. Link
- Bjerre Knudsen L, et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010;151(4):1473-86. PMID 20203154. Link
- Madsen LW, et al. GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology. 2012;153(3):1538-47. PMID 22234463. Link
- Eli Lilly and Company. Zepbound (tirzepatide) US prescribing information, revised 08/2026. Link
This is general information, not medical or legal advice. Rules vary by state and change. Confirm your own facts with counsel.