Is there a link between pancreatic cancer and Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide (exenatide), liraglutide (liraglutide), and dulaglutide (dulaglutide)?

From the Guidelines

There is no conclusive link between GLP-1 receptor agonists, such as exenatide, liraglutide, and dulaglutide, and pancreatic cancer, and these medications can continue to be prescribed for patients with type 2 diabetes or obesity according to standard guidelines. The most recent and highest quality study, published in 2024 1, found that while there have been reports of acute pancreatitis associated with the use of exenatide, the current guidelines from the American Association of Clinical Endocrinologists recommend using GLP-1 receptor agonists with caution in patients with a history of pancreatitis. However, this does not necessarily imply a link between GLP-1 receptor agonists and pancreatic cancer.

Key Points to Consider

• The LEADER trial showed a benefit in cardiovascular outcomes with GLP-1 receptor agonists, with a significant reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction or stroke 1.
• The SUSTAIN 6 trial also confirmed the cardiovascular benefit of GLP-1 receptor agonists in patients with type 2 diabetes at high cardiovascular risk 1.
• A recent randomised double-blind study found that semaglutide reduced the primary cardiovascular endpoint in non-diabetic patients with pre-existing cardiovascular disease and BMI > 27 1.
• The most common adverse effects of GLP-1 receptor agonists are nausea, vomiting, and diarrhea, which are dose-dependent and can be managed with slow titration and dose adjustment 1.
• Regulatory agencies, including the FDA and EMA, have reviewed the available data and concluded that a causal relationship between GLP-1 receptor agonists and pancreatic cancer has not been established, as noted in the context of other studies 1.

Clinical Implications

• Healthcare providers should discuss the benefits and potential risks of GLP-1 receptor agonists with patients, and patients should report any unusual symptoms such as persistent abdominal pain, unexplained weight loss, or jaundice.
• Ongoing monitoring and research continue to evaluate the long-term safety of these medications.
• GLP-1 receptor agonists can be a valuable treatment option for patients with type 2 diabetes or obesity, and their use should be guided by standard clinical guidelines and patient-specific factors.

From the Research

Pancreatic Cancer and GLP-1 Receptor Agonists

The relationship between pancreatic cancer and Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide, liraglutide, and dulaglutide, has been investigated in several studies.

• The use of GLP-1 receptor agonists has been associated with an increased risk of pancreatitis and pancreatic cancer in some studies 2.
• However, other studies have found no significant association between GLP-1 receptor agonists and the risk of pancreatitis or pancreatic cancer 3, 4.
• Some studies have even suggested that GLP-1 receptor agonists may be associated with a lower risk of pancreatic cancer 5, 6.

Key Findings

• A 2011 study found that the use of GLP-1 receptor agonists increased the odds ratio for reported pancreatitis and pancreatic cancer compared to other therapies 2.
• A 2022 study found that GLP-1 agonists were associated with a significantly lower risk of pancreatic cancer compared to metformin 5.
• A 2023 meta-analysis found no association between GLP-1 receptor agonists and the risk of pancreatitis or pancreatic cancer 4.
• A 2024 historical cohort study found no support for an increased pancreatic cancer incidence over 7 years following the start of GLP-1RA treatment 6.

Study Variations

• The studies varied in their design, population, and follow-up period, which may contribute to the inconsistent findings.
• Some studies had limitations, such as potential biases and confounding variables, which may affect the accuracy of the results.
• The evidence suggests that the relationship between GLP-1 receptor agonists and pancreatic cancer is complex and may depend on various factors, including the specific medication, population, and follow-up period 2, 3, 5, 4, 6.