What are the potential adverse effects of Ozempic (semaglutide) in an adult patient with type 2 diabetes?

Adverse Effects of Ozempic (Semaglutide)

Most Common Adverse Effects

Gastrointestinal side effects are the predominant adverse reactions with Ozempic, occurring in the majority of patients but typically being dose-dependent and transient. 1, 2, 3

Gastrointestinal Effects

• Nausea occurs in 15.8-20.3% of patients (compared to 6.1% with placebo), making it the most frequent adverse effect 3
• Vomiting affects 5.0-9.2% of patients (versus 2.3% with placebo) 3
• Diarrhea occurs in 8.5-8.8% of patients (compared to 1.9% with placebo) 3
• Abdominal pain affects 5.7-7.3% of patients (versus 4.6% with placebo) 3
• Constipation occurs in 3.1-5.0% of patients (compared to 1.5% with placebo) 3

The majority of gastrointestinal reactions occur during dose escalation, and 3.1-3.8% of patients discontinue treatment due to these effects. 3 Slow up-titration significantly reduces the severity of these symptoms. 1, 2

Less Common Gastrointestinal Effects

• Dyspepsia (2.7-3.5%), eructation (1.1-2.7%), flatulence (0.4-1.5%), gastroesophageal reflux disease (1.5-1.9%), and gastritis (0.4-0.8%) 3
• Esophageal reflux results from delayed gastric emptying 2
• Severe constipation with potential progression to small bowel obstruction or ileus 2

Serious Adverse Events Requiring Monitoring

Pancreatitis

• Acute pancreatitis has been reported in clinical trials, though causality has not been definitively established. 2 Up-titrate slowly and discontinue if pancreatitis is suspected; do not restart if confirmed. 1

Gallbladder Disease

• Cholelithiasis (gallstones) was reported in 1.5% of patients treated with Ozempic 0.5 mg and 0.4% with placebo. 3
• Cholecystitis also occurs at increased rates and requires monitoring. 2

Hypoglycemia

• When used as monotherapy, severe hypoglycemia did not occur (0%). 3
• When combined with basal insulin, severe hypoglycemia occurred in 1.5% of patients on the 1 mg dose. 3
• When co-administered with sulfonylureas, severe hypoglycemia occurred in 0.8-1.2% of patients. 3
• The hypoglycemia risk increases significantly when Ozempic is combined with insulin, sulfonylureas, or glinides, requiring dose reduction of these agents. 1, 2

Renal Effects

• Acute kidney injury and worsening chronic renal failure can occur, particularly from dehydration secondary to severe gastrointestinal effects. 2
• Monitor renal function closely when initiating or escalating doses, especially in patients with pre-existing kidney disease. 2

Cardiovascular Effects

• Acute myocardial infarction has been reported in clinical trials. 2
• Elevated heart rate is a common side effect requiring monitoring. 2

Diabetic Retinopathy Complications

Diabetic retinopathy complications were reported with injectable semaglutide, although it is unclear if this is a direct effect of the drug or due to other factors such as rapid improvement in blood glucose control. 1 Patients with a history of diabetic retinopathy should be monitored closely for progression. 2

Laboratory Abnormalities

Pancreatic Enzymes

• Patients exposed to Ozempic had a mean increase from baseline in amylase of 13% and lipase of 22%, changes not observed in placebo-treated patients. 3

Injection Site Reactions

Injection site reactions (e.g., discomfort, erythema) were reported in 0.2% of Ozempic-treated patients. 3

Absolute Contraindications

• Personal or family history of medullary thyroid cancer 1, 2
• Personal or family history of multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2
• Pregnancy or breastfeeding 1, 2
• History of serious hypersensitivity reaction to semaglutide 1

Relative Contraindications and Cautions

• Severe gastroparesis: Not recommended in patients with clinically meaningful gastroparesis, as Ozempic may delay gastric emptying 1, 2
• Prior gastric surgery: Care should be taken in patients with prior gastric surgery, including bariatric surgery 1
• History of pancreatitis: Use with caution 2

Drug Interactions and Special Considerations

Delayed Gastric Emptying Effects

• Ozempic may delay absorption of concomitantly administered oral medications due to delayed gastric emptying. 2
• Particular attention should be paid to medications with narrow therapeutic indices (e.g., warfatin). 2
• For oral hormonal contraceptive users, add or switch to non-oral contraception for 4 weeks after initiation and each dose escalation. 2

Weight Loss

• Weight loss is an expected effect and should be monitored. 1

Dose Modifications for Safety

• Up-titrate slowly to reduce nausea and vomiting. 1
• Discontinue if pancreatitis is suspected and do not restart if pancreatitis is confirmed. 1
• When combined with insulin or sulfonylureas, reduce the dose of these medications to prevent hypoglycemia. 2

Monitoring Recommendations

• Monitor for nausea, vomiting, diarrhea, headache, weakness, or dizziness 1
• Monitor for hypoglycemia when given with insulin, sulfonylureas, or glinides 1
• Monitor weight loss 1
• Monitor for injection site reactions 1
• Monitor renal function closely, especially with severe gastrointestinal symptoms that could lead to dehydration 2
• Monitor for signs of gallbladder disease (right upper quadrant pain, nausea) 2
• Monitor for persistent severe abdominal pain (pancreatitis) 2
• Monitor heart rate 2

Common Pitfalls to Avoid

• Do not advance doses too rapidly: This increases gastrointestinal side effects significantly 1, 2
• Do not ignore peri-operative aspiration risk: Retained gastric contents are documented even after extended fasting periods 2
• Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors: This is not recommended 2
• Do not overlook the need to reduce insulin or sulfonylurea doses: Failure to do so significantly increases hypoglycemia risk 1, 2