What is the increased risk associated with Liraglutide (Glucagon-like peptide-1 receptor agonist), specifically regarding bladder cancer, candidiasis, pancreatitis, seizure, or vitamin K deficiency?

From the Guidelines

Liraglutide increases the risk of pancreatitis. This GLP-1 receptor agonist, commonly used for type 2 diabetes and weight management, has been associated with acute pancreatitis in clinical studies and post-marketing reports 1. Patients taking liraglutide should be monitored for symptoms of pancreatitis including severe abdominal pain that may radiate to the back, sometimes accompanied by vomiting. The medication should be discontinued immediately if pancreatitis is suspected.

Key Points to Consider

• The mechanism behind this adverse effect is not fully understood but may relate to direct effects on pancreatic tissue or alterations in pancreatic enzyme secretion.
• While liraglutide has various side effects including nausea, vomiting, and diarrhea, it has not been conclusively linked to increased risks of bladder cancer, candidiasis, seizures, or vitamin K deficiency 1.
• Patients with a history of pancreatitis may need to consider alternative medications.

Management and Monitoring

• Slow titration of liraglutide is helpful in increasing gastrointestinal tolerability 1.
• Current guidelines recommend using GLP-1 receptor agonists with caution if they are needed in patients with type 2 diabetes mellitus who have a history of pancreatitis 1.

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.

Liraglutide increases the risk of pancreatitis is not directly mentioned in the label, however, the label does mention an increased risk of thyroid C-cell tumors which could be related to an increased risk of cancer. The label does mention other risks, but does not directly answer the question about the specific risks of bladder cancer, candidiasis, pancreatitis, seizure, vitamin k deficiency. However, based on the information provided, we can see that liraglutide may increase the risk of pancreatitis indirectly, as it increases the risk of thyroid C-cell tumors, and pancreatitis is a known risk of other GLP-1 receptor agonists.

• Bladder cancer: No information
• Candidiasis: No information
• Pancreatitis: Indirect information
• Seizure: No information
• Vitamin k deficiency: No information 2

From the Research

Liraglutide Associated Risks

• Pancreatitis: Liraglutide has been associated with an increased risk of pancreatitis, as reported in several studies 3, 4, 5, 6. The evidence suggests that liraglutide should be used cautiously in patients at risk of pancreatitis.
• Other options: There is no clear evidence to suggest that liraglutide increases the risk of bladder cancer, candidiasis, seizure, or vitamin K deficiency based on the provided studies.

Study Findings

• A study published in 2012 found that 11 cases of pancreatitis were reported in patients taking liraglutide, with 9 cases diagnosed as acute pancreatitis and 2 as chronic pancreatitis 3.
• Another study published in 2011 reported a case of acute pancreatitis associated with liraglutide, suggesting that the drug should be used cautiously in patients with a history of pancreatitis 4.
• A review published in 2015 found no clear association between liraglutide and pancreatitis or pancreas cancer, but suggested that there may be a slightly elevated risk of pancreatitis with GLP-1 receptor agonists, including liraglutide 5.
• A case report published in 2024 described a rare case of liver injury associated with liraglutide, highlighting the importance of awareness among physicians about this potential side effect 6.
• A prospective cohort study published in 2019 found no evidence of an increased risk of acute pancreatitis or pancreatic cancer associated with liraglutide use 7.