Side Effects
Gastrointestinal adverse effects are the most common, particularly during dose escalation. They tend to be transient and usually improve within several weeks at a stable dose.
Frequent (greater than 20% incidence):
- Nausea (39%)
- Diarrhea (21%)
Very Common (10 to 20% incidence):
- Constipation (19%)
- Vomiting (16%)
- Headache
- Decreased appetite
- Dyspepsia
Common (1 to 10% incidence):
- Abdominal pain
- Fatigue
- Dizziness
- Injection site reactions
- Gastroesophageal reflux
- Flatulence
Rare but Serious:
- Pancreatitis (0.3% in clinical trials; discontinue immediately if suspected)
- Gallbladder disease and cholelithiasis (increased incidence with rapid weight loss)
- Acute kidney injury (usually secondary to severe dehydration from GI effects)
- Hypoglycemia (primarily when combined with insulin or sulfonylureas)
- Thyroid C-cell tumors (observed in rodent studies at clinically relevant exposures; human relevance uncertain)
- Allergic reactions and anaphylaxis (rare)
Liraglutide carries a boxed warning regarding thyroid C-cell tumor risk based on animal data. In rodent studies, liraglutide caused dose-dependent thyroid C-cell tumors, including medullary thyroid carcinoma (MTC). It is contraindicated in individuals with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Mitigation strategies include strict adherence to the titration schedule, eating smaller and more frequent meals, avoiding high-fat and greasy foods, staying well hydrated, and eating slowly. Delaying dose escalation by one week is recommended if side effects are intolerable at a given dose level.