Is there an increased cancer risk associated with Glucagon-like peptide (GLP)?

From the Guidelines

There is no established increased cancer risk with GLP-1 receptor agonists, and current evidence does not support a causal link between these medications and cancer development in humans. The most recent and highest quality study, the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial 1, found that the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the exenatide group and the placebo group.

Key Points

• Early concerns about pancreatic cancer and thyroid cancer were raised during initial drug development, but subsequent large-scale clinical trials and post-marketing surveillance have not confirmed these risks 1.
• Some preclinical studies have suggested potential anti-cancer effects of GLP-1 based therapies.
• The FDA and other regulatory agencies continue to monitor the safety of these medications, but at present, patients should not avoid GLP-1 medications due to cancer concerns.
• The benefits of these medications for diabetes management and weight loss typically outweigh theoretical risks.

Special Considerations

• Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 should not use these medications as a precautionary measure.
• Always discuss individual risk factors with your healthcare provider when considering any medication.
• The EXSCEL trial 1 and other studies have demonstrated the safety and efficacy of GLP-1 receptor agonists in reducing cardiovascular events, with no significant increase in cancer risk.

From the FDA Drug Label

A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03,0.2,1.0, and 3.0 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD of 1. 8 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1.0 and the 3.0 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively. C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3. 0 mg/kg/day group. A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075,0.25 and 0. 75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 8-times the human exposure, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0. 75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075,0.25, and 0. 75 mg/kg/day groups, respectively. A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075,0.25, and 0. 75 mg/kg/day groups, respectively.

The GLP-1 receptor agonist liraglutide has been associated with an increased risk of thyroid C-cell tumors in animal studies. Key findings include:

• Benign thyroid C-cell adenomas were seen in mice and rats treated with liraglutide.
• Malignant thyroid C-cell carcinomas were also observed in mice and rats treated with liraglutide. However, the human relevance of these findings is unknown and has not been determined by clinical studies or nonclinical studies 2.

From the Research

Increased Cancer Risk with GLP-1 Receptor Agonists

• There is no direct evidence in the provided studies that suggests an increased cancer risk with GLP-1 receptor agonists 3, 4, 5, 6, 7.
• The studies primarily focus on the efficacy and safety of GLP-1 receptor agonists in the treatment of type 2 diabetes, highlighting their benefits in improving glycemic control, promoting weight loss, and reducing cardiovascular risk factors.
• Some studies mention the potential for GLP-1 receptor agonists to have beneficial effects on beta-cell function and possibly even neurodegenerative diseases, but none of them discuss a potential increased cancer risk 3, 7.
• It is essential to note that the provided studies do not investigate the long-term effects of GLP-1 receptor agonists on cancer risk, and therefore, no conclusions can be drawn from the available evidence 4, 5, 6.

Key Findings on GLP-1 Receptor Agonists

• GLP-1 receptor agonists have been shown to be effective in improving glycemic control, with some agents being more effective than others in reducing HbA1c levels 4, 6.
• These agents also promote weight loss and have beneficial effects on cardiovascular risk factors, such as blood pressure and lipid parameters 3, 6.
• The most common adverse events associated with GLP-1 receptor agonists are gastrointestinal disturbances, including nausea, vomiting, and diarrhea, which are usually transient and resolve over time 5, 7.