What are the potential side effects of Ozempic (semaglutide) and how can they be managed in patients with diabetes or obesity?

Latest Side Effects of Ozempic (Semaglutide)

Most Critical Recent Safety Concerns

Semaglutide carries a 38% higher risk of serious adverse events compared to placebo, with the most concerning issues being gastrointestinal complications, gallbladder disease, pancreatitis, and perioperative aspiration risk from delayed gastric emptying. 1

Common Gastrointestinal Side Effects

Nausea, vomiting, diarrhea, constipation, and abdominal pain remain the most frequent adverse effects, occurring in the majority of patients but typically being dose-dependent and more pronounced during initial treatment or dose escalation. 1

• These gastrointestinal symptoms are transient in most cases and can be minimized through slow dose titration starting at 0.25 mg weekly for 4 weeks. 1
• To manage nausea and vomiting, reduce meal size; to reduce reflux symptoms, limit alcohol and carbonated drinks; and avoid high-fat diets to help with constipation. 1
• Esophageal reflux occurs as a result of delayed gastric emptying, which is a fundamental mechanism of the medication. 1

Serious Adverse Events Requiring Immediate Attention

Pancreatitis

Stop using Ozempic immediately and seek medical care if you develop severe, persistent abdominal pain that radiates to your back, with or without vomiting. 2

• Acute pancreatitis has been reported in clinical trials, though causality remains unestablished. 1
• Use with caution in patients with a history of pancreatitis. 1

Gallbladder Disease

There is an increased risk of cholelithiasis (gallstones) and cholecystitis requiring ongoing monitoring. 1

• The mechanism relates to rapid weight loss and altered bile composition. 1
• Monitor for right upper quadrant pain, fever, or jaundice during treatment. 1

Acute Kidney Injury

Dehydration from severe gastrointestinal side effects can precipitate acute kidney injury, particularly in patients with pre-existing kidney disease. 1

• Monitor renal function closely when initiating or escalating doses, especially in patients reporting severe gastrointestinal reactions. 1
• Ensuring adequate fluid intake is crucial to prevent dehydration-related kidney injury. 1

Critical Perioperative Safety Issue

Retained gastric contents are documented even after extended fasting periods, creating significant aspiration risk during anesthesia. 1

• Cases have been reported in patients who stopped semaglutide 4-6 days before surgery. 1
• Increased residual gastric content was found in 24.2% of semaglutide users versus 5.1% of controls undergoing endoscopy, despite 10-14 day discontinuation and 12-hour fasting. 1
• For elective surgery requiring anesthesia, discontinue semaglutide for at least 3 weeks (three half-lives) before the procedure. 1

Cardiovascular Considerations

While semaglutide reduces cardiovascular risk in appropriate populations, acute myocardial infarction has been reported in clinical trials. 1

• In the SELECT trial, major cardiovascular events occurred in 6.5% of those treated with semaglutide compared with 8% in the placebo group, representing a 20% risk reduction. 1
• Elevated heart rate is a common side effect requiring monitoring. 1

Other Notable Adverse Effects

Diabetic Retinopathy Complications

Patients with a history of diabetic retinopathy should be monitored closely for progression when using semaglutide. 1

Hypoglycemia Risk

The risk of hypoglycemia increases significantly when semaglutide is used with insulin or insulin secretagogues (sulfonylureas, glinides). 1, 2

• Signs include dizziness, blurred vision, sweating, confusion, shakiness, and fast heartbeat. 2
• Dose reduction of insulin or sulfonylureas is required when initiating semaglutide. 1

Injection Site Reactions and Other Effects

• Injection site reactions occur with subcutaneous administration. 1
• Insomnia and risk of suicidal ideation have been reported as potential side effects. 1
• Dysaesthesia (abnormal sensations) was reported in 18.9% of patients on the higher 7.2 mg dose versus 4.9% on 2.4 mg. 3

Absolute Contraindications

Semaglutide is absolutely contraindicated in the following situations: 1, 2

• Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) - carries FDA Black Box Warning based on rodent studies showing thyroid C-cell tumors. 1
• Pregnancy or breastfeeding. 1
• Severe hypersensitivity reaction to semaglutide. 2

Relative Contraindications and Cautions

• Not recommended in patients with clinically meaningful gastroparesis, as semaglutide delays gastric emptying and will worsen symptoms. 1
• Use with caution in patients with prior gastric surgery, including bariatric surgery. 1
• Patients with severe renal impairment require careful monitoring due to increased risk of gastrointestinal side effects and potential dehydration. 1
• Caution in patients with untreated closed-angle glaucoma. 1

Critical Drug Interactions

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

• Semaglutide may delay absorption of concomitantly administered oral medications, particularly those with narrow therapeutic index like warfarin. 1
• Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors. 1

Essential Monitoring Recommendations

Regular monitoring should include: 1

• Renal function, especially in patients with pre-existing kidney disease or experiencing severe gastrointestinal side effects
• Signs of pancreatitis (persistent severe abdominal pain)
• Gallbladder disease symptoms (right upper quadrant pain, fever)
• Blood pressure (may require antihypertensive adjustment as weight decreases)
• Diabetic retinopathy progression in at-risk patients
• Assessment at least monthly for the first 3 months, then at least quarterly thereafter

Common Pitfalls to Avoid

• Never start at high doses - always begin at 0.25 mg weekly and titrate slowly every 4 weeks to minimize gastrointestinal side effects. 1
• Do not ignore perioperative aspiration risk - discontinue at least 3 weeks before elective surgery requiring anesthesia. 1
• Do not overlook dehydration risk - severe gastrointestinal symptoms can lead to acute kidney injury, particularly in patients with pre-existing renal disease. 1
• Do not forget to reduce insulin/sulfonylurea doses when initiating semaglutide to prevent hypoglycemia. 1