From the Guidelines
GLP-1 receptor agonists have not been conclusively linked to causing cancer in humans, and current evidence suggests they are generally safe regarding cancer risk, with some studies indicating potential anti-cancer properties. The most recent and highest quality study, published in 2024 1, provides a comprehensive review of the clinical pharmacology and implications of GLP-1 receptor agonists, including their safety profile. While there were early concerns based on rodent studies showing increased thyroid C-cell tumors, particularly with liraglutide, this effect appears specific to rodents due to their higher concentration of GLP-1 receptors in thyroid tissue compared to humans.
Key Points to Consider
- For patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, GLP-1 receptor agonists are contraindicated.
- Some observational studies have suggested a possible increased risk of pancreatic cancer, but larger studies and meta-analyses have not confirmed this association.
- GLP-1 medications may potentially reduce the risk for certain cancers by addressing obesity, a known cancer risk factor.
- Ongoing long-term studies continue to monitor cancer outcomes in patients using these medications, but current evidence supports their safety profile regarding cancer risk for most patients.
Management and Safety
The study 1 also highlights the importance of managing common adverse effects of GLP-1 receptor agonists, such as nausea, vomiting, and diarrhea, which are dose-dependent and more frequent with short-acting drugs. Slow titration is helpful in increasing gastrointestinal tolerability. Acute pancreatitis, a rare adverse effect, has been linked to the use of exenatide, and current guidelines recommend using GLP-1 receptor agonists with caution in patients with a history of pancreatitis.
Cardiovascular Benefits
The LEADER trial and the SUSTAIN 6 trial, cited in the study 1, demonstrate the cardiovascular benefits of GLP-1 receptor agonists, including a reduced risk of cardiovascular death, non-fatal myocardial infarction, or stroke. These benefits are significant and support the use of GLP-1 receptor agonists in patients with type 2 diabetes mellitus at high cardiovascular risk.
Peri-Operative Management
The study 1 also discusses the use of GLP-1 receptor agonists in the peri-operative management of hyperglycemia, showing an insulin-sparing effect and significant decreases in plasma glucose. The GLOBE study and other trials cited in the study demonstrate the efficacy of GLP-1 receptor agonists in cardiac and non-cardiac surgery, highlighting their potential as an alternative to insulin in the peri-operative period.
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 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.
Key findings:
- Liraglutide, a GLP-1 receptor agonist, was associated with an increased risk of thyroid C-cell tumors (both benign and malignant) in mice and rats.
- The human relevance of these findings is unknown and has not been determined by clinical studies or nonclinical studies 2.
- Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1 receptor.
- It is essential to exercise caution when using liraglutide, especially in patients with a history of thyroid cancer or multiple endocrine neoplasia syndrome type 2.
From the Research
GLP-1 and Cancers
There is no direct evidence in the provided studies to suggest a link between GLP-1 receptor agonists and cancers.
Available Information
- The studies focus on the efficacy and safety of GLP-1 receptor agonists in the treatment of type 2 diabetes, their effects on glucose control, weight loss, and cardiovascular risk factors 3, 4, 5, 6, 7.
- They compare the effectiveness of different GLP-1 receptor agonists, such as exenatide, liraglutide, dulaglutide, and semaglutide, in reducing HbA1c levels and body weight 4, 7.
- The studies also discuss the common adverse events associated with GLP-1 receptor agonists, including gastrointestinal disorders, nausea, vomiting, and diarrhea 4, 5, 6, 7.
Limitations
- None of the provided studies investigate the relationship between GLP-1 receptor agonists and cancers.
- Therefore, there is no evidence to support or refute a potential link between GLP-1 receptor agonists and cancers based on the provided studies.