Wegovy (Semaglutide) Side Effects
Most Common Side Effects
Gastrointestinal symptoms are the predominant side effects of Wegovy, occurring in the majority of patients but typically being transient and dose-dependent. 1, 2
Gastrointestinal Effects
- Nausea (28-44% of patients), diarrhea (21-30%), and constipation (11-24%) are the most frequently reported adverse effects 3
- Vomiting, abdominal pain, esophageal reflux, and flatulence also commonly occur 1
- These effects are most pronounced during initial treatment or dose escalation and typically subside with time 1, 4
- Slow dose titration minimizes these gastrointestinal side effects 1, 2
- Approximately 4.5% of patients discontinue treatment due to gastrointestinal events 4
Other Common Side Effects
Serious Adverse Events
Clinical trials demonstrate a 38% higher risk of serious adverse events with semaglutide compared to placebo. 2, 5
Pancreatitis
- Pancreatitis has been reported in clinical trials, though causality has not been definitively established 1, 6
- Discontinue Wegovy immediately if pancreatitis is suspected (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting) 6
- Consider alternative therapies in patients with a history of pancreatitis 6
Gallbladder Disease
- Increased risk of cholelithiasis (gallstones) and cholecystitis requiring monitoring 1, 2, 5
- May cause gallstone-related complications 1
Acute Kidney Injury
- Risk of acute kidney injury from dehydration, particularly in patients with pre-existing kidney disease 1, 5
- Use caution when initiating or increasing doses in patients with kidney disease due to increased gastrointestinal side effects and potential dehydration 1
Cardiovascular Events
- Acute myocardial infarction and gastroenteritis reported as serious adverse events 2, 5
- However, Wegovy has demonstrated cardiovascular benefits, reducing major adverse cardiovascular events (6.5% vs 8% with placebo) 2
Diabetic Retinopathy Complications
- In patients with diabetes, more diabetic retinopathy complications occurred with semaglutide (3.0%) compared to placebo (1.8%) 6
- Risk is particularly elevated in patients with pre-existing diabetic retinopathy (8.2% vs 5.2% with placebo) 6
Absolute Contraindications
Wegovy is absolutely contraindicated in the following situations: 6
- Personal or family history of medullary thyroid carcinoma (MTC) 1, 2, 6
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1, 2, 6
- Known hypersensitivity to semaglutide or product components 6
- Pregnancy or breastfeeding 1, 2
Black Box Warning
- FDA Black Box Warning: Risk of thyroid C-cell tumors based on rodent studies (dose-dependent thyroid adenomas and carcinomas in mice and rats) 2, 6
- Human relevance has not been determined 1, 6
- Counsel patients about symptoms of thyroid tumors: neck mass, dysphagia, dyspnea, persistent hoarseness 6
Important Precautions and Warnings
Hypoglycemia Risk
- Increased risk of hypoglycemia when used with insulin, sulfonylureas, or glinides 1, 2
- Dose reduction of these concomitant medications may be required 2
Gastroparesis and Delayed Gastric Emptying
- Not recommended in patients with clinically meaningful gastroparesis 2
- May delay absorption of concomitantly administered oral medications 2, 5
- For patients using oral hormonal contraceptives: switch to non-oral contraceptive method or add barrier method for 4 weeks after initiation and 4 weeks after each dose escalation due to reduced efficacy from delayed gastric emptying 1, 2
Renal Considerations
- Can be used with caution in severe renal impairment or end-stage renal disease, unlike exenatide which is contraindicated if eGFR <30 mL/min/1.73 m² 1, 2
- Monitor renal function closely, especially with severe gastrointestinal side effects that could lead to dehydration 2
Other Precautions
- Risk of suicidal ideation has been reported 2, 5
- Caution in patients with prior gastric surgery, including bariatric surgery 1, 2
- Risk of acute angle-closure glaucoma 1
- Potential for severe allergic reactions 2
Clinical Pearls for Management
Dose Titration Strategy
- Start with 0.25 mg subcutaneously once weekly for 4 weeks (this dose is for initiation only, not effective for weight control) 6
- Increase to 0.5 mg weekly after 4 weeks 6
- Maximum dose is 2.4 mg once weekly for weight management 1, 6
Minimizing Side Effects
- Reduce meal size to manage nausea and vomiting 2
- Limit alcohol and carbonated drinks to reduce reflux symptoms 2
- Avoid high-fat diets to help with constipation 2
- Use gradual dose titration to minimize gastrointestinal effects 2, 5