What are the cancer risks associated with Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide (Byetta) or liraglutide (Victoza), in patients with type 2 diabetes?

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Last updated: December 11, 2025 • View editorial policy

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GLP-1 Receptor Agonists and Cancer Risk

GLP-1 receptor agonists do not increase the overall risk of malignancy in patients with type 2 diabetes and may actually reduce the risk of certain gastrointestinal cancers, but they are absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2). 1, 2

Absolute Contraindications Related to Cancer

The only cancer-related contraindication for GLP-1 receptor agonists is:

  • Personal or family history of medullary thyroid carcinoma 1, 2
  • Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2

This contraindication stems from preclinical rodent studies showing thyroid C-cell tumors, though this has not been demonstrated in humans. 1

Overall Cancer Risk: Evidence from Large Trials and Meta-Analyses

No increased risk of overall malignancy has been demonstrated across multiple large cardiovascular outcomes trials and meta-analyses:

  • A comprehensive meta-analysis of 34 trials including 50,452 patients found no increase in malignant neoplasm formation with GLP-1 receptor agonists compared to placebo or other interventions (OR 1.04,95% CI 0.94-1.15; p = 0.46). 3

  • Individual agent analysis showed no increased cancer risk for:

    • Liraglutide (OR 1.08,95% CI 0.91-1.27) 3
    • Exenatide (OR 1.00,95% CI 0.86-1.16) 3
    • Semaglutide (OR 0.89,95% CI 0.35-2.22) 3
    • Albiglutide (OR 1.07,95% CI 0.23-4.88) 3

  • Trials lasting longer than 3 years confirmed no increase in neoplasia risk (OR 1.03,95% CI 0.92-1.15). 3

Specific Cancer Types

Pancreatic Cancer

No increased risk of pancreatic cancer has been demonstrated in clinical trials:

  • A meta-analysis of once-weekly GLP-1 receptor agonists in 16,090 patients found no increased tumor risk (RR 1.02,95% CI 0.74-1.41). 4
  • Another meta-analysis found no association between exenatide (OR 0.86,95% CI 0.29-2.60) or liraglutide (OR 1.35,95% CI 0.70-2.59) and cancer risk. 5

Important caveat: While no increased risk has been shown, exenatide has not been studied in patients with a history of pancreatitis, and the FDA label recommends considering other antidiabetic therapies in such patients. 6

Thyroid Cancer

No increased risk of thyroid cancer (other than the theoretical MTC risk):

  • Liraglutide was not associated with increased thyroid cancer risk (OR 1.54,95% CI 0.40-6.02). 5
  • No thyroid malignancies were reported with exenatide in clinical trials. 5
  • Calcitonin elevations (a marker for MTC) to >20 ng/L occurred in only 0.7% of liraglutide-treated patients versus 0.3% of placebo patients, with unclear clinical significance. 7

Gastrointestinal Cancers: Potential Protective Effect

Emerging evidence suggests GLP-1 receptor agonists may actually reduce the risk of gastric and esophageal cancers:

  • In a large database analysis of 146,277 matched patients with type 2 diabetes, those on GLP-1 receptor agonists had significantly lower rates of:
    • Gastric cancer (0.05% vs. 0.13%, p < 0.0001) 8
    • Esophageal cancer (0.04% vs. 0.13%, p < 0.0001) 8

This protective effect persisted even after excluding patients with obesity, GERD, and other confounding factors. 8

Monitoring Recommendations

Routine cancer screening beyond standard guidelines is not required for patients on GLP-1 receptor agonists:

  • Monitor calcitonin levels if clinically indicated, though routine screening is not recommended. 7
  • The incidence of acute pancreatitis, pancreatic cancer, and medullary thyroid carcinoma did not differ significantly between GLP-1 receptor agonist users and controls in major trials. 1

Clinical Decision Algorithm

Before initiating GLP-1 receptor agonist therapy:

  1. Screen for absolute contraindications: personal or family history of MTC or MEN2 2
  2. If contraindications present: Do not prescribe; choose alternative therapy
  3. If no contraindications: Proceed with GLP-1 receptor agonist therapy without additional cancer-related concerns 2

During ongoing therapy:

  • Continue standard age-appropriate cancer screening per general population guidelines 3
  • No additional thyroid or pancreatic cancer surveillance is required beyond clinical judgment 7

Bottom Line

The current evidence strongly supports that GLP-1 receptor agonists can be used without safety concerns related to malignant neoplasia in patients with type 2 diabetes, provided they do not have a personal or family history of MTC or MEN2. 3 The cardiovascular and metabolic benefits of these agents far outweigh any theoretical cancer concerns in appropriately selected patients. 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

GLP-1 Receptor Agonists in Hashimoto's Thyroiditis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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