Effect of Incretin Analogues and Dipeptidyl-peptidase-IV inhibitors on the risk of thyroid cancer

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/107225
• EU PAS number:
  EUPAS107225
• Study ID:
  107225
• Official title and acronym:
  Effect of Incretin Analogues and Dipeptidyl-peptidase-IV inhibitors on the risk of thyroid cancer
• DARWIN EU® study:
  No
• Study countries:
  United States
• Study description:
  Incretin based therapies are commonly used as second-line antihyperglycemic drugs in the treatment of type 2 diabetes mellitus. They promote glucose dependent insulin secretion, suppress glucagon secretion, slow gastric emptying, and promote satiety or potentiate the action of incretin hormones by blocking DPP-IV – the enzyme responsible for the degradation of incretin hormones. Activation of the GLP-1 receptor has been shown to cause thyroid C-cell hyperplasia and C-cell tumors in carcinogenicity studies in preclinical studies using rodents prompting the U.S. Food and Drug Administration (FDA) to issue a warning regarding medullary thyroid cancer for long-acting GLP-1RA. Still, the relevance of these findings in humans is questionable, as there is a discrepancy in the level of expression and biology of GLP-1 receptors in the thyroid between rodents and primates. Currently, there remains uncertainty about the risk of thyroid cancer associated with the use of incretin (GLP-1)-based therapies with data from clinical and observational studies showing conflicting results. Some studies have reported no increased risk of thyroid cancer with the use of GLP-1RA relative to placebo or other antihyperglycemic drugs, while a recent study found an increased risk of all thyroid cancer and medullary thyroid cancer, particularly after 1-3 years of treatment. Most of the existing studies suffer from methodological issues, including short durations of follow-up, limited lag period, uncertainty about valid ascertainment of outcomes, diagnostic suspicion, insufficient confounding control, incomplete covariate ascertainment and inadequate power. Additionally, most studies so far have only focused on the effect of exenatide and liraglutide on thyroid cancer. This work, therefore, aims to address these issues, and contribute critical evidence to inform clinical decision-making by exploring the effect of GLP-1RA and DPP-IV inhibitors on thyroid cancer incidence.
• Study status:
  Finalised

Research institution and networks

Institutions

University of North Carolina at Chapel Hill

Study timelines

Date when funding contract was signed

Planned: 29/06/2022

Actual: 29/06/2022

Study start date

Planned: 29/06/2022

Actual: 29/06/2022

Date of final study report

Planned: 31/12/2024

Actual: 17/10/2023

Sources of funding

Other

More details on funding

National Institute on Aging at NIH

Study protocol

Initial protocol

Effect of Incretin Analogs on risk of thyroid cancer

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable