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. 2024 Jun 13;14(6):687. doi: 10.3390/biom14060687

Table 1.

Summary of clinical evidence about GLP-1 RAs and the risk of developing thyroid cancer. RCT: randomized clinical trial; ETR: estimated treatment ratio; CI: confidence interval; MTC: medullary thyroid cell carcinoma; aHR: adjusted hazard ratio; PRR: proportional reporting ratio; GLP-1 RAs: Glucagon-like Peptide-1 receptor agonists; aHR: adjusted hazard ratio; PTC: papillary thyroid carcinoma; SGLT2i: Sodium-glucose cotransporter 2 inhibitors; wHR: weighted hazard ratio. Green: no increase in the risk of thyroid cancer; red: increased risk of thyroid cancer.

Study Characteristics of the Study Findings
LEADER
2018 [55]		 RCT
liraglutide (n = 4364) vs. placebo (n = 4321)
Follow-up: 3.5–5 years
  • No increase in calcitonin concentrations in the liraglutide group
    • ○
      male: ETR 1.03 95% CI 1.0–1.06, p = 0.068
    • ○
      female: ETR 1.00 95% CI 0.97–1.02, p = 0.67

  • No cases of MTC in liraglutide group
Mali et al.
2020 [58]		 Case/non-case analysis on report EudraVigilance
11,243 cases of thyroid cancer (236 involved GLP-1 RAs)
until 30 January 2020
  • Exenatide, liraglutide, and dulaglutide met the criteria to generate safety signals for thyroid cancer
    • ○
      Liraglutide: PRR 27.5 95% CI 22.7–33.3
    • ○
      Exenatide: PRR 22.5 95% CI 17.9–28.3
    • ○
      Dulaglutide: PRR 13.1 95% CI 9.4–18.3
Bezin et al.
2023 [56]		 Nested case–control analysis
subjects with thyroid cancer (n = 2562) vs. controls (n = 45,184)
  • Increased risk of all thyroid cancer and MTC in subjects receiving GLP-1 RAs for 1–3 years
    • ○
      All thyroid cancer: aHR 1.58 95% CI 1.27–1.95
    • ○
      MTC: aHR per MTC 1.78, 95%CI 1.04–3.05
Silverii et al.
2023 [62]		 Meta-analysis of 64 RCT
GLP-1 RAs (n = 46,228) vs. any comparator (n = 38,399)
  • Increased risk of all thyroid cancer in GLP-1 RA users
    • ○
      MH-OR 1.52 95%CI 1.01–2.29, p = 0.04, I2 = 0%

  • No significant association with PTC or MTC
Bea et al.
2023 [60]		 Population-based cohort study
New users of GLP-1 RAs (n = 21,722) vs. new users of SGLT2i (n = 326,993)
  • GLP-1 RAs are not associated with an increased risk of thyroid cancer
    • ○
      wHR 0.98 95%CI 0.62–1.53
Feier et al.
2024 [61]		 Systematic review of 10 RCT (use of semaglutide)
n = 14,550 with 7830 receiving semaglutide

  • Incidence of thyroid cancer less than 1% in semaglutide users à no significant risk