Common Side Effects of Wegovy (Semaglutide)
Gastrointestinal side effects are the predominant adverse events with Wegovy, occurring in the majority of patients, with nausea being most common (44% of patients), followed by diarrhea (30%), vomiting (25%), and constipation (24%). 1, 2
Gastrointestinal Side Effects (Most Common)
The following GI side effects occur significantly more frequently than placebo and are typically dose-dependent, most pronounced during initial treatment or dose escalation 1, 3:
- Nausea - affects approximately 44% of patients (vs. 16% with placebo) 4
- Diarrhea - occurs in approximately 30% of patients (vs. 16% with placebo) 4
- Vomiting - affects approximately 25% of patients (vs. 6% with placebo) 4
- Constipation - occurs in approximately 24% of patients (vs. 11% with placebo) 4
- Abdominal pain and discomfort 1, 5
- Esophageal reflux 1, 3
- Flatulence 1
Critical clinical pearl: These GI side effects are typically transient, mild-to-moderate in severity (98% of cases), and subside with time, occurring most frequently during or shortly after dose escalation. 4, 6 Slow dose titration minimizes these effects 1, 3. Only 4.3-4.5% of patients permanently discontinue treatment due to GI adverse events 4, 6.
Serious Adverse Events
Wegovy carries a 38% higher risk of serious adverse events compared to placebo, including 1, 3:
- Gallbladder disease - including cholelithiasis (gallstones) and cholecystitis, requiring monitoring 1, 2
- Pancreatitis - acute pancreatitis confirmed in 0.3 cases per 100 patient-years (vs. 0.2 with comparators) 1, 7
- Acute kidney injury - particularly from dehydration secondary to severe GI effects, especially in patients with pre-existing kidney disease 1, 3
- Acute myocardial infarction - reported in clinical trials 1
Other Notable Side Effects
- Injection site reactions 1
- Insomnia - documented as a side effect requiring monitoring 3
- Elevated heart rate - requires monitoring 1
- Suicidal ideation - reported in clinical trials 1, 3
- Diabetic retinopathy complications - particularly in patients with pre-existing diabetic retinopathy (8.2% vs. 5.2% placebo) 7
Black Box Warning and Contraindications
Wegovy carries an FDA Black Box Warning regarding thyroid C-cell tumors based on rodent studies. 1, 7 The medication is absolutely contraindicated in 1, 7:
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Pregnancy or breastfeeding 1
- Known hypersensitivity to semaglutide 7
Management Strategies
To minimize side effects, implement gradual dose titration starting at 0.25 mg weekly for 4 weeks, then escalating to 0.5 mg, with maximum dose of 2.4 mg weekly for weight management. 1, 7 Additional management strategies include 1:
- Reduce meal size to manage nausea and vomiting
- Limit alcohol and carbonated drinks to reduce reflux symptoms
- Avoid high-fat diets to help with constipation
- Monitor renal function closely, especially with severe GI side effects that could lead to dehydration 1, 3
Important contraceptive consideration: For patients using oral hormonal contraceptives, switch to non-oral contraception or add barrier method for 4 weeks after initiation and each dose escalation due to delayed gastric emptying affecting absorption. 1