Assessment of thyroid cancer risk associated with glucagon‐like peptide 1 receptor agonist use

Aims Published literature has raised concerns regarding a causal association between glucagon‐like peptide 1 receptor agonist (GLP‐1RA) use and thyroid cancer risk in adults. In this analysis, we evaluated the association between thyroid cancer risk and GLP‐1RA use. Materials and Methods Our evaluation included data from (i) 93 liraglutide or semaglutide phase 2 and 3 clinical trials, of which six were cardiovascular outcome trials (CVOTs); (ii) post‐marketing surveillance from the Novo Nordisk safety database (evaluating data for liraglutide and semaglutide); and (iii) the US Merative™ MarketScan® Commercial Database. Hazard ratios (HRs) were estimated for overall thyroid cancer risk for treatment groups in the clinical trials and for individuals with type 2 diabetes treated with any GLP‐1RAs versus sodium–glucose cotransporter‐2 inhibitors (SGLT2is) for the real‐world data. Results Data from all clinical trials across 101 732 participants (totalling 206 950 patient‐years of exposure [PYE]) reported low numbers of thyroid cancer events; across all trials, HRs were 1.70 (95% confidence interval [CI] 0.99, 3.03) and 1.83 (0.70, 6.71) for pooled GLP‐1RA versus pooled placebo and active comparator, respectively. For CVOTs, the HR (95% CI) for pooled GLP‐1RA versus pooled placebo was 1.41 (0.72, 2.81). Post‐marketing surveillance data showed a low thyroid cancer reporting rate of 0.001 cases/100 PYE and did not support an association between liraglutide or semaglutide exposure and the number of thyroid cancer events. Analysis of the US Merative™ MarketScan® Commercial Database reported an HR of 0.87 (95% CI 0.58, 1.29) for the occurrence of thyroid cancer in individuals using any GLP‐1RAs versus SGLT2is. Conclusions The totality of data analysed did not suggest an association between liraglutide or semaglutide use and thyroid cancer risk in adults.