What are the side effects of Ozempic (semaglutide)?

Ozempic (Semaglutide) Side Effects

Ozempic commonly causes gastrointestinal side effects—particularly nausea, vomiting, diarrhea, constipation, and abdominal pain—which are dose-dependent and typically most pronounced during initial treatment or dose escalation, but also carries a 38% higher risk of serious adverse events compared to placebo, including pancreatitis, gallbladder disease, and acute myocardial infarction. 1

Most Common Side Effects (Reported in ≥5% of Patients)

Gastrointestinal Effects (Predominant)

• Nausea is the most frequent adverse effect, occurring in the majority of patients 2
• Vomiting is very common and dose-dependent 1, 2
• Diarrhea occurs frequently and may lead to dehydration 1, 2
• Constipation is a common complaint 1, 2
• Abdominal pain affects many patients 1, 2
• Esophageal reflux and flatulence also commonly occur 3

Clinical Pearl: These gastrointestinal symptoms are typically transient and can be minimized through slow dose titration 1, 3. To manage nausea, reduce meal size; to reduce reflux, limit alcohol and carbonated drinks; avoid high-fat diets to help with constipation 1.

Serious Adverse Events (38% Higher Risk vs. Placebo)

Pancreatic Complications

• Pancreatitis is a serious risk requiring immediate discontinuation 1, 3, 2
• Stop Ozempic immediately if severe abdominal pain occurs that will not go away, with or without vomiting, and the pain may radiate from abdomen to back 2
• Use with caution in patients with a history of pancreatitis 1

Gallbladder Disease

• Cholelithiasis (gallstones) risk is doubled (OR 2.06) 1, 3, 4
• Cholecystitis requires monitoring 1, 3
• Regular monitoring for gallbladder disease is advised 1, 3

Renal Complications

• Acute kidney injury can occur, particularly from dehydration due to gastrointestinal side effects 1, 3, 2
• Patients with pre-existing kidney disease require careful monitoring 1, 3
• Diarrhea, nausea, and vomiting may cause fluid loss leading to worsening kidney problems 2
• It is critical to maintain adequate hydration to reduce dehydration risk 2

Cardiovascular Events

• Acute myocardial infarction has been reported in clinical trials 1, 3
• Cardiac arrhythmia/tachycardia may occur; if symptomatic, consider beta blockers 1
• However, semaglutide reduces cardiovascular death, heart attack, and stroke in adults with obesity and cardiovascular disease (6.5% vs 8% in placebo) 1

Ophthalmologic Complications

• Changes in vision should be reported immediately 2
• Diabetic retinopathy complications can occur, particularly with rapid glucose lowering 1, 3
• Patients with existing diabetic retinopathy require close monitoring for progression 1

Hypoglycemia

• Risk increases significantly when combined with insulin, sulfonylureas, or glinides 1, 3, 2
• Dose reduction of these medications may be required 1, 3
• Signs include dizziness, blurred vision, anxiety, sweating, slurred speech, confusion, shakiness, weakness, headache, fast heartbeat, and feeling jittery 2

Absolute Contraindications

Thyroid Cancer Risk

• Personal or family history of medullary thyroid carcinoma (MTC) is an absolute contraindication 1, 3, 2
• Multiple endocrine neoplasia syndrome type 2 (MEN 2) is an absolute contraindication 1, 3, 2
• FDA Black Box Warning exists regarding thyroid C-cell tumors based on rodent studies 1

Pregnancy and Breastfeeding

• Pregnancy is an absolute contraindication 1
• Breastfeeding is an absolute contraindication 1
• Safety has not been established in these populations 1

Other Notable Side Effects

Gastroparesis

• Delayed gastric emptying occurs due to mechanism of action 3, 5
• Not recommended in patients with clinically meaningful gastroparesis 1
• Patients with severe gastroparesis may experience worsened symptoms 1
• May affect absorption of concomitantly administered oral medications 3

Oral Contraceptive Considerations

• Consider switching to non-oral contraceptive method or adding barrier method for 4 weeks after initiation and after each dose escalation due to delayed gastric emptying potentially reducing efficacy 1

Other Reported Effects

• Injection site reactions can occur 1
• Insomnia has been documented as a side effect 3
• Risk of suicidal ideation has been reported 1
• Serious allergic reactions including itching, rash, or difficulty breathing require immediate discontinuation and medical attention 2

Monitoring Recommendations

Essential monitoring includes: 1, 3

• Regular renal function assessment, especially with severe gastrointestinal symptoms
• Gastrointestinal symptom surveillance
• Signs of pancreatitis (severe abdominal pain)
• Gallbladder disease monitoring
• Blood glucose levels as directed by healthcare provider 2
• Hemoglobin A1C with regular blood tests 2
• Sleep disturbances, particularly during initial titration 3

Critical Pitfalls to Avoid

• Do not share your Ozempic pen with others, even if the needle has been changed, as this can transmit serious infections 2
• Do not mix insulin and Ozempic together in the same injection 2
• Change injection sites with each injection to avoid site reactions 2
• If dose is missed, take within 5 days; if more than 5 days have passed, skip and resume regular schedule 2
• Discontinuation rates are significant due to gastrointestinal side effects (OR 3.77 for GI-related discontinuation) 4