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Thyroid cancer: a bound rather than a verdict

Across 437,077 patients the hazard ratio was 0.93, and the authors bound it: no more than a 31% increase in relative risk. For medullary cancer specifically, the interval runs from 0.37 to 3.86.

Ruth Alvarez6 min read
Thyroid cancer risk, against DPP-4 inhibitors1.0all thyroid cancermedullary only437,077 patients. The second interval is the honest one.

The thyroid warning on these drugs comes from rodent studies, and it has followed the class into every patient leaflet since. Whether it translates to people has taken a decade and several very large datasets to address, and the answer is more interesting than either “yes” or “no” — it is a bound — the same discipline this site applies to a published price in what happens when you read a price twice.

What was compared

A nationwide cohort study used registry data from three countries to compare 145,410 patients treated with GLP-1 receptor agonists against 291,667 treated with DPP-4 inhibitors[1]. Mean follow-up was 3.9 years in the first group and 5.4 in the second.

Seventy-six thyroid cancers occurred in the GLP-1 group, an incidence rate of 1.33 per 10,000 person-years, against 184 in the comparator group at 1.46. The hazard ratio was 0.93 (95% CI 0.66 to 1.31), and the rate difference was −0.13 events per 10,000 person-years (95% CI −0.61 to 0.36). Both groups had type 2 diabetes, which is a different population from the one most sellers here serve — a gap that also limits the results in GLP-1 and cancer risk.

The subgroup the warning is about

Medullary thyroid cancer is the specific tumor the rodent data raised and the labeling names. In this study its hazard ratio was 1.19, with a confidence interval from 0.37 to 3.86.

That interval spans a two-thirds reduction and a near-quadrupling. It is what happens when a very rare cancer is looked for in a cohort that is large but not large enough, and it means the study cannot settle the question the warning exists for. A comparison against SGLT-2 inhibitors gave 1.16 (0.65 to 2.05) for thyroid cancer overall, which is consistent and equally imprecise.

What a buyer does with this

The practical answer is unchanged by the study, because the labeling already says it: anyone with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 should not take these drugs. That is a contraindication rather than a risk calculation, and it is the sort of thing an intake form should ask about.

Whether it does is a separate question. Most sellers tracked here publish nothing about what their intake asks or who reviews the answers, which we count in what sellers will not tell you and list seller by seller in the questions they leave open. A contraindication only works if somebody checks for it, and the wider pattern of claims that outrun their evidence is in what the semaglutide trials are worth.

Frequently asked

Do these drugs cause thyroid cancer?
Across 437,077 patients the hazard ratio was 0.93 (95% CI 0.66 to 1.31). The authors bound their conclusion: the upper limit was consistent with no more than a 31% increase in relative risk.
What about medullary thyroid cancer specifically?
The hazard ratio was 1.19 with an interval from 0.37 to 3.86 — too wide to rule much in or out, on a cancer rare enough that this cohort could not resolve it.
Who should avoid these drugs?
The labeling contraindicates them for anyone with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. That is unchanged by this study.
How common is thyroid cancer here at all?
About 1.33 events per 10,000 person-years in the treated group, against 1.46 in the comparator — rare enough that relative risks translate to very small absolute numbers.

Sources

  1. [1] Pasternak B, et al. (2024). Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study BMJ. PMID 38683947

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