Side Effects
Gastrointestinal adverse effects are the most common, particularly during dose escalation:
Frequent (greater than 20% incidence):
- Nausea (14–58%)
- Diarrhea
- Vomiting
- Constipation
Very Common (10–20% incidence):
- Abdominal pain
- Fatigue
- Dizziness
- Dyspepsia
Common (1–10% incidence):
- Injection site reactions
- Gastroesophageal reflux
Rare but Serious:
- Pancreatitis (discontinue immediately if suspected)
- Gallbladder disease and cholelithiasis
- Acute kidney injury (usually secondary to dehydration from GI effects)
- Hypoglycemia (primarily when combined with insulin or sulfonylureas)
- Thyroid C-cell tumors (observed in rodent studies; human relevance uncertain)
Semaglutide carries a boxed warning regarding thyroid C-cell tumor risk based on animal data. It is contraindicated in individuals with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.
Mitigation strategies include strict adherence to titration schedules, eating smaller meals, avoiding high-fat foods, and maintaining adequate hydration.“The gastrointestinal side effect profile is dose-dependent and self-limiting in most patients, which is precisely why the titration schedule exists. Clinically, the patients who struggle most are those who escalate too quickly — adherence to the four-week intervals at each dose level is the single most important factor in tolerability.”
