(P-125) Risk of Thyroid Cancer with the Use of GLP-1 Receptor Agonists

Background: Pre-clinical studies suggested a risk of medullary thyroid C-cell cancer with GLP-1 receptor agonists (RA).

Objectives: To evaluate the risk of thyroid cancer with the use of GLP-1 RA in a real-world setting.

Methods: A nested case-control analysis was performed using the French national healthcare insurance system SNDS (“Système National des Données de Santé”) database, which records anonymized individual level data including sociodemographic data, outpatient healthcare dispensed, hospital discharge summaries, and registration status for a list of 30 long term diseases (LTD). Patients pharmacologically treated for a type 2 diabetes between 2006 and 2018 were included in the cohort. All thyroid cancers were identified using ICD-10 codes from hospital discharge and medical procedures between 2014 and 2018. Medullary thyroid cancers were studied in a secondary analysis. Exclusion criteria were history of cancer, radiotherapy or pregnancy in the years before the index date. Exposure to GLP-1 RA was measured within the 6 years preceding a 6-month lag-time period and considered as follows: i) current users, and ii) cumulative duration of use based on defined daily dose (≤1, 1 to 3, >3 years). Cases were matched with up to 20 controls on age, sex, and length of diabetes, using the risk-set sampling procedure. The risk of thyroid cancer related to the use of GLP-1 analogues was estimated using a conditional logistic regression adjusted on hypo and hyperthyroidism, other antidiabetic drugs and social deprivation index.

Results: Among the 3,746,672 patients included in the source population, 2,562 cases and 45,184 controls were included. Almost two thirds were female (67%), and median age was 64 [IQR: 56; 71] years. Half of the patients (50% of cases and 56% of controls) had a type 2 diabetes for more than 8 years. The current use of GLP-1 RA was associated with thyroid cancer (HR 1.45, IC95% [1.22; 1.73]), compared to other antidiabetic drugs. Considering cumulative duration of use, the association reached statistical significance for 1 to 3 years of GLP-1 RA use (HR 1.63 [1.31; 2.02]) and more than 3 years (HR 1.30 [1.00; 1.69]). Increased risks were also found for medullary thyroid cancers (HR 1.82 [1.19; 2.79], and 2.22 [1.32; 3.75], respectively). When GLP-1 RA analysed separately, the association was retrieved for each the three GLP-1 RA drugs (exenatide, liraglutide, dulaglutide).

Conclusions: The present study found an increased risk of all thyroid cancer and medullary thyroid cancers with the use of GLP-1 RA, in particular after 1 to 3 years of treatment.