Most Common Side Effects of OZEMPIC
The most common side effects of OZEMPIC (semaglutide) are gastrointestinal: nausea, vomiting, diarrhea, abdominal pain, and constipation, occurring in ≥5% of patients. 1
Primary Gastrointestinal Side Effects
The FDA-approved labeling explicitly identifies the five most frequent adverse reactions 1:
- Nausea - Most commonly reported GI side effect 2, 1
- Vomiting - Occurs frequently, particularly during dose escalation 2, 1
- Diarrhea - Common but typically functional and improves with continued use 2, 1
- Abdominal pain - Reported in ≥5% of patients 2, 1
- Constipation - Can range from mild to severe 2, 1
These gastrointestinal effects are dose-dependent and typically most pronounced during initial treatment or dose escalation 2, 3. The American Diabetes Association emphasizes that these symptoms are generally transient 2.
Key Management Strategy
Slow dose titration is the primary strategy to minimize gastrointestinal side effects 2, 3. The standard titration schedule starts at 0.25 mg weekly for 4 weeks, then 0.5 mg, then 1 mg if needed 2.
Practical Management Tips
- Reduce meal size to help manage nausea and vomiting 2
- Limit alcohol and carbonated drinks to reduce reflux symptoms 2
- Avoid high-fat diets to help with constipation 2
- Ensure adequate fluid intake to prevent dehydration from GI symptoms 2
Additional Common Side Effects
Beyond the primary five, other notable side effects include:
- Esophageal reflux - Results from delayed gastric emptying 2, 3
- Injection site reactions - Occur with subcutaneous administration 2
- Elevated heart rate - Requires monitoring 2
- Insomnia - Documented in clinical guidelines as a potential side effect 3
Serious Adverse Events Requiring Awareness
While less common, OZEMPIC carries a 38% higher risk of serious adverse events compared to placebo 2, 3, including:
- Gallbladder disease (cholelithiasis and cholecystitis) - Increased risk requiring monitoring 2, 3, 4
- Pancreatitis - Stop medication if severe abdominal pain occurs 2, 1
- Acute kidney injury - Particularly from dehydration secondary to severe GI effects 2, 1
- Diabetic retinopathy complications - Monitor patients with existing retinopathy closely 2, 4
Critical Monitoring Recommendations
The American Diabetes Association recommends 2:
- Monthly assessment for the first 3 months, then quarterly thereafter
- Monitor renal function closely when initiating or escalating doses, especially with severe GI symptoms
- Check for signs of gallbladder disease periodically (right upper quadrant pain, nausea)
- Monitor for pancreatitis symptoms (severe abdominal pain radiating to back)
Important Clinical Pitfall
For patients using oral hormonal contraceptives, consider switching to non-oral contraception or adding a barrier method for 4 weeks after initiation and each dose escalation 2. This is due to delayed gastric emptying potentially affecting oral contraceptive absorption.
Hypoglycemia Risk
OZEMPIC has very low intrinsic hypoglycemia risk when used alone 2. However, when combined with insulin or sulfonylureas, reduce the dose of these medications to prevent hypoglycemia 2, 1.