What are the adverse effects of Ozempic (semaglutide)?

Ozempic (Semaglutide) Adverse Effects

Ozempic commonly causes gastrointestinal side effects—particularly nausea, vomiting, diarrhea, abdominal pain, and constipation—and carries a 38% higher risk of serious adverse events compared to placebo, including pancreatitis, gallbladder disease, and acute kidney injury. 1, 2

Common Gastrointestinal Side Effects

The most frequent adverse effects occur in the gastrointestinal system and are reported in ≥5% of patients:

• Nausea (43.9% vs 16.1% placebo) is the most common side effect, typically mild-to-moderate and transient 2, 3
• Diarrhea (29.7% vs 15.9% placebo) occurs frequently during treatment 3
• Vomiting (24.5% vs 6.3% placebo) is common, particularly during dose escalation 3
• Abdominal pain affects a significant proportion of patients 2
• Constipation (24.2% vs 11.1% placebo) is reported frequently 3
• Esophageal reflux occurs as a result of delayed gastric emptying 1, 4

These gastrointestinal effects are dose-dependent, occur most frequently during or shortly after dose escalation, and 99.5% are non-serious. 3 Gradual dose titration significantly minimizes these symptoms. 1

Serious Adverse Events

Clinical trials demonstrate a 38% increased risk of serious adverse events (RR 1.38,95% CI 1.10-1.73) compared to placebo: 1

Pancreatitis

• Acute pancreatitis has been reported in clinical trials, though causality remains unestablished 1, 2
• Discontinue Ozempic immediately if pancreatitis is suspected and do not restart if confirmed 2
• Patients should be monitored for severe abdominal pain that radiates to the back, with or without vomiting 2

Gallbladder Disease

• Increased risk of cholelithiasis (gallstones) and cholecystitis requiring monitoring 1, 4
• This represents a class effect of GLP-1 receptor agonists related to weight loss and altered bile composition 5

Acute Kidney Injury

• Risk of acute kidney injury and worsening chronic renal failure, particularly from dehydration secondary to severe gastrointestinal effects 1, 2
• Monitor renal function closely when initiating or escalating doses, especially in patients with pre-existing kidney disease 4, 2
• Patients experiencing severe nausea, vomiting, or diarrhea require fluid replacement to prevent dehydration-induced renal injury 2

Cardiovascular Events

• Acute myocardial infarction has been reported in clinical trials 1
• Elevated heart rate is a common side effect requiring monitoring 1
• Cardiac arrhythmia/tachycardia may occur and warrant beta-blocker consideration if symptomatic 4

Black Box Warning: Thyroid C-Cell Tumors

Ozempic carries an FDA Black Box Warning for risk of thyroid C-cell tumors based on rodent studies, though human relevance remains undetermined. 2

• Absolutely contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2, 1
• Counsel patients regarding potential risk and symptoms of thyroid tumors 2

Diabetic Retinopathy Complications

• Worsening of diabetic retinopathy has been reported, particularly in patients with existing retinopathy 2, 6
• Patients with history of diabetic retinopathy should be monitored closely, especially if also treated with insulin 2, 5
• Risk appears related to rapid improvement in glycemic control 5

Gastroparesis and Delayed Gastric Emptying

• Ozempic delays gastric emptying, which can worsen symptoms in patients with pre-existing gastroparesis 4, 7
• Not recommended in patients with clinically meaningful gastroparesis 4
• May cause severe constipation, small bowel obstruction, or ileus progression 1
• Affects absorption of concomitantly administered oral medications, particularly those with narrow therapeutic index like warfarin 1, 2

Hypoglycemia Risk

• Ozempic has very low intrinsic hypoglycemia risk due to glucose-dependent insulin secretion 4
• Risk increases significantly when combined with insulin secretagogues (sulfonylureas, glinides) or insulin 1, 2
• Consider lowering doses of insulin or secretagogues when initiating Ozempic 2

Other Notable Adverse Effects

• Injection site reactions occur with subcutaneous administration 1
• Insomnia has been documented as a side effect 8
• Suicidal ideation has been reported in clinical trials 1
• Nonarteritic anterior ischemic optic neuropathy (NAION) is an emerging concern 6

Contraindications

Absolute contraindications include: 2, 4

• Personal or family history of medullary thyroid carcinoma or MEN 2
• Known hypersensitivity to semaglutide or product components
• Pregnancy or breastfeeding (discontinue at least 2 months before planned pregnancy due to long washout period) 2, 4

Critical Management Considerations

Only 4.3% of patients permanently discontinue treatment due to gastrointestinal adverse events, and weight loss is largely independent of GI side effects. 3 This indicates that most patients can successfully continue therapy with appropriate management:

• Start at 0.25 mg once weekly and titrate slowly over at least 4 weeks 2
• If more than 5 days pass after a missed dose, skip it and resume regular schedule 2
• Reduce meal size and avoid high-fat foods to minimize nausea 4
• Limit alcohol and carbonated drinks to reduce reflux 4
• Never share pens between patients even if needle is changed due to infection risk 2

For oral hormonal contraceptive users, add or switch to non-oral contraception for 4 weeks after initiation and each dose escalation due to delayed gastric emptying affecting absorption. 1