Risks of Retaglutide (GLP-1 Receptor Agonist)
Retaglutide, like other GLP-1 receptor agonists, primarily carries risks of gastrointestinal side effects, potential pancreatitis, gallbladder disease, and thyroid C-cell tumors, with additional concerns including acute kidney injury and increased heart rate. 1, 2
Common Adverse Effects
Gastrointestinal Side Effects
- Nausea, vomiting, and diarrhea are the most frequently reported adverse events 2, 3
- Constipation may also occur 4
- These effects are typically dose-dependent, with higher doses associated with increased risk 3
- Background treatment with metformin significantly increases the risk of nausea (P=.04) and vomiting (P=.0009) 3
Other Common Side Effects
- Injection site reactions 4
- Headache and nasopharyngitis 4
- Elevated heart rate (up to 6.7 beats/min with retaglutide) 5
Serious Potential Risks
Pancreatitis
- Pancreatitis has been reported in clinical trials of GLP-1 receptor agonists 1
- Treatment should be discontinued if pancreatitis is suspected 6
Gallbladder Disease
- May cause cholelithiasis (gallstones) and gallstone-related complications 1
Thyroid Concerns
- Black box warning: Risk of thyroid C-cell tumors observed in rodents (human relevance not determined) 1
- Contraindicated in patients with personal or family history of medullary thyroid carcinoma or MEN2 6
Kidney-Related Risks
- Use caution in patients with kidney disease when initiating or increasing dose due to potential risk of acute kidney injury 1, 6
- Several case reports have linked GLP-1 receptor agonists, particularly exenatide, with acute kidney injury primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea 4
- Regular monitoring of kidney function is recommended, especially in patients with pre-existing renal impairment 6
Gastrointestinal Disorders
- Risk of severe constipation and small bowel obstruction/ileus progression 1
- May delay absorption of oral medications 1
Special Considerations
Hypoglycemia Risk
- Low risk when used alone or with metformin/thiazolidinediones 4
- Increased risk when combined with insulin or sulfonylureas; dose reduction of these medications may be necessary 1, 4
Medication Interactions
- Contraindicated for use in combination with monoamine oxidase inhibitors 1
- Should not be used with DPP-4 inhibitors 6
- May affect absorption of other oral medications due to delayed gastric emptying 1
Risk Mitigation Strategies
- Start with the lowest dose and gradually titrate to minimize gastrointestinal side effects 6, 7
- Monitor kidney function regularly, especially when initiating therapy or increasing doses 6
- Consider reducing doses of concomitant insulin or sulfonylureas to minimize hypoglycemia risk 4
- Recommend smaller food portions to help manage gastrointestinal effects 6
- Use with caution in patients at risk for dehydration, and consider reducing diuretic doses 6