Adverse Effects of GLP-1 Receptor Agonists

Common Gastrointestinal Adverse Effects

Nausea occurs in up to 44% of patients, most common with semaglutide, which is dose-dependent and typically more frequent with short-acting than long-acting formulations 1, 2, 3
Vomiting is reported in 13-18% of patients, highest with semaglutide, and is dose-dependent 1
Diarrhea affects 13-18% of patients, more common with long-acting formulations, and is dose-dependent 1
Constipation occurs in approximately 10-30% of patients 3
Dyspepsia is reported in 6-7% of patients 1
Gastroesophageal reflux is reported in 2-3% of patients 1

Starting GLP-1 receptor agonist at low dose and titrating upward slowly can improve gastrointestinal tolerability 1
Reducing meal size can minimize symptoms 1
Limiting alcohol and carbonated drinks can reduce reflux 1
Avoiding high-fat diet can reduce constipation 1
Most GI symptoms are transient and diminish over several weeks to months 4

Heart rate increase is typically approximately 5 bpm 4
Cardiac arrhythmia/tachycardia may require monitoring and consideration of beta blockers 1
GLP-1 receptor agonists have demonstrated cardiovascular benefits in patients with type 2 diabetes at high cardiovascular risk 1, 5

Acute pancreatitis is linked to exenatide, with liraglutide showing highest risk 1
Gallbladder disorders, including cholelithiasis requiring cholecystectomy, can occur 1, 6
Thyroid concerns, including risk of thyroid C-cell tumors in rodents, have been reported 7, 6

Patients with history of pancreatitis should use GLP-1 receptor agonists with caution 1
Patients with gastroparesis should avoid GLP-1 receptor agonists 1
Patients at risk for thyroid C-cell tumors should not use GLP-1 receptor agonists 4, 7
GLP-1 receptor agonists can be used in chronic kidney disease with appropriate dose adjustments, but exenatide is not recommended if eGFR <30 ml/min/1.73m² 4, 7

GLP-1 receptor agonists do not cause hypoglycemia when used alone or with metformin/thiazolidinediones 4
When combined with insulin or sulfonylureas, dose reductions of these medications may be necessary to avoid hypoglycemia 4, 7