GLP-1 medicines and thyroid cancer: the Scandinavian cohort study

Why this study matters

Whether GLP-1 medicines such as semaglutide (Wegovy, Ozempic) raise the risk of thyroid cancer has been a long-running question. An earlier French study found an association, and this site covers it on a separate page. The Scandinavian study used a different and generally stronger design to test the same question in a very large population. Canadian readers who have seen headlines about GLP-1 medicines and thyroid cancer will want to know how the two studies fit together.

Who was in the study

The researchers used nationwide health and cancer registers from Denmark, Norway and Sweden covering 2007 to 2021. The main comparison included 145410 people who started a GLP-1 receptor agonist and 291667 people who started a DPP-4 inhibitor. DPP-4 inhibitors are a different class of diabetes medicine. An additional analysis compared GLP-1 users with people who started an SGLT2 inhibitor, another diabetes medicine class.

Average follow-up was 3.9 years in the GLP-1 group (standard deviation 3.5 years) and 5.4 years in the DPP-4 group (standard deviation 3.5 years). The summary we reviewed does not report the age range.

What the researchers did

This was a cohort study, which follows groups of people over time without assigning them to a treatment by chance. It used what is called an active-comparator new-user design. New-user means everyone was followed from the day they started the medicine. Active-comparator means GLP-1 users were compared with people starting a different medicine for the same condition, rather than with people taking nothing. This helps to make the two groups more alike, because both had reached the same point in their diabetes care.

Thyroid cancers were identified from national cancer registers. The researchers used a statistical method called propensity score weighting to balance the two groups on many measured characteristics, and then used Cox regression to estimate hazard ratios. A hazard ratio compares how often an event happens in one group with another over time. A value of 1 means no difference.

What they found

Thyroid cancer developed in 76 of 145410 GLP-1 users, an incidence rate of 1.33 events per 10000 person-years, and in 184 of 291667 DPP-4 inhibitor users, a rate of 1.46 per 10000 person-years. Person-years add up the time each person was followed.

The hazard ratio for thyroid cancer with GLP-1 medicines compared with DPP-4 inhibitors was 0.93, with a 95% confidence interval of 0.66 to 1.31 (R32-C119). A confidence interval is the range in which the true value is likely to sit. Because it includes 1, the study did not find a clear increase or decrease. The rate difference was -0.13 events per 10000 person-years (95% CI -0.61 to 0.36).

The authors note that in the main comparison, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk. The estimate for medullary thyroid cancer, a rare type, has a very wide interval because so few cases occurred.

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. Even with a strong design, differences between the groups that were not measured could affect the result. This is called residual confounding.
• Average follow-up was 3.9 years for GLP-1 users. The study cannot say what happens over a lifetime of use.
• Medullary thyroid cancer is rare, and the study had too few cases to give a precise estimate for it.
• The study does not fully rule out a small increase in risk. The confidence interval allows for up to a 31% relative increase.
• This study and the earlier French case-control study disagree. They used different comparison groups and different methods, and neither settles the question on its own.
• Most people starting these medicines in the study period were likely being treated for diabetes. The summary we reviewed does not describe people using the medicines for weight management without diabetes.
• The summary we reviewed does not state who funded the study.

What it means in Canada

For Canadian readers, this study is reassuring but not final. It found no clear increase in thyroid cancer over an average of 3.9 years in a very large population, using a design that reduces some common biases. 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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