GLP-1 medicines and thyroid cancer: a French insurance-data study

Why this study matters

Whether GLP-1 medicines such as semaglutide (Wegovy, Ozempic) affect the risk of thyroid cancer, including a rare type called medullary thyroid cancer, is a long-standing safety question. This French study is one of the most cited pieces of evidence suggesting a link. Canadian readers should know what it found and, just as important, what it cannot prove. A later Scandinavian study reached a different conclusion, and this site covers it on a separate page.

Who was in the study

The researchers used the French national health insurance database, known as SNDS. The cohort included adults with type 2 diabetes who were treated with second-line diabetes medicines between 2006 and 2018. Second-line means medicines added after a first treatment, usually metformin. Thyroid cancers diagnosed between 2014 and 2018 were identified from hospital discharge records and medical procedures.

The analysis compared 2562 people who developed thyroid cancer with 45184 matched control subjects who did not. The summary we reviewed does not report the age range.

What the researchers did

This was a nested case-control study. Within a large group of people followed over time, the researchers identified everyone who developed thyroid cancer (the cases). For each case, they selected up to 20 people from the same cohort who had not developed thyroid cancer (the controls), matched on age, sex and how long they had had diabetes. This is a way of studying a rare outcome in a large population without following everyone in detail.

Exposure to GLP-1 medicines was measured over the 6 years before a 6-month lag period. A lag period means the researchers ignored prescriptions in the months right before the diagnosis, because a medicine started just before a cancer is found is unlikely to have caused it. Exposure was classed as current use and by total time on the medicine: 1 year or less, 1 to 3 years, or more than 3 years.

The researchers adjusted their results for goitre, underactive thyroid, overactive thyroid, other diabetes medicines and a social deprivation index. No one was assigned to a treatment by chance, so this was not a randomized trial.

What they found

Use of a GLP-1 medicine for 1 to 3 years was associated with a higher rate of all thyroid cancer, with an adjusted hazard ratio of 1.58 and a 95% confidence interval of 1.27 to 1.95 (R32-C118). A hazard ratio compares how often an event happens in one group with another over time. A value of 1 means no difference. A confidence interval is the range in which the true value is likely to sit. Because the whole range is above 1, the association was statistically clear.

For medullary thyroid cancer, a rare type, the adjusted hazard ratio for 1 to 3 years of use was 1.78 (95% CI 1.04 to 3.05). The lower end of that range is close to 1, so the estimate is less precise.

The summary we reviewed does not report the results for use of 1 year or less, or for use of more than 3 years. It also does not report how many people out of 1000 developed thyroid cancer in each group.

Side effects and people who stopped

This study looked only at thyroid cancer. It does not report other side effects or how many people stopped their medicine.

What this study does not tell you

• This is an observational study. It shows an association, not cause and effect.
• People taking GLP-1 medicines may have had more medical visits and more scans, which can lead to more thyroid cancers being found. This is called detection bias.
• Other differences between users and non-users that the researchers could not measure may explain part or all of the association. This is called residual confounding.
• The comparison group was people not using GLP-1 medicines, rather than people using a different specific medicine. A later Scandinavian study that compared GLP-1 users with users of another diabetes medicine found no clear increase. The two studies disagree.
• Everyone had type 2 diabetes. The findings do not directly describe people using these medicines for weight management without diabetes.
• The summary we reviewed does not state who funded the study.

What it means in Canada

This study is one reason thyroid cancer remains a discussion point for GLP-1 medicines. It does not prove the medicines cause thyroid cancer, and a later study with a stronger design did not find the same signal. For how these medicines are used in Canada, see semaglutide in Canada and tirzepatide in Canada. For coverage questions, see public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

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