What are the side effects of Ozempic (semaglutide)?

Side Effects of Ozempic (Semaglutide)

The most common side effects of Ozempic are gastrointestinal in nature—specifically nausea, vomiting, diarrhea, abdominal pain, and constipation—occurring in ≥5% of patients, with these effects being dose-dependent and typically most pronounced during initial treatment or dose escalation. 1, 2

Common Gastrointestinal Side Effects

The FDA-approved labeling identifies the following as the most frequent adverse reactions:

• Nausea, vomiting, diarrhea, abdominal pain, and constipation are reported in ≥5% of patients treated with Ozempic 1
• These gastrointestinal effects are typically dose-dependent and more pronounced during initial treatment or dose escalation 2, 3
• Esophageal reflux and flatulence also commonly occur due to delayed gastric emptying 2, 1
• Gradual dose titration minimizes these gastrointestinal side effects and is the recommended management strategy 2, 3

Clinical Pearl: If a patient tolerates a submaximal dose well and achieves adequate response, continuing that dose long-term is acceptable rather than escalating to avoid worsening GI symptoms 2

Serious Adverse Events

Ozempic carries a 38% higher risk of serious adverse events compared to placebo, including several potentially life-threatening conditions 2, 3:

Pancreatitis

• Stop Ozempic immediately if severe abdominal pain occurs that will not go away, with or without vomiting, as this may indicate pancreatitis 1
• Pain may radiate from the abdomen to the back 1
• While acute pancreatitis has been reported in clinical trials, definitive causality remains unestablished 2

Gallbladder Disease

• Increased risk of cholelithiasis (gallstones) and cholecystitis requiring monitoring 2, 3
• This is a class effect of GLP-1 receptor agonists and warrants clinical vigilance 2

Acute Kidney Injury

• Risk of acute kidney injury and worsening chronic renal failure, particularly from dehydration secondary to severe gastrointestinal effects 2, 1
• In patients with pre-existing kidney disease, diarrhea, nausea, and vomiting may cause fluid loss leading to kidney problems worsening 1
• Monitor renal function closely when initiating or escalating doses, especially in patients reporting severe gastrointestinal reactions 2
• It is important to drink fluids to help reduce the chance of dehydration 1

Cardiovascular Events

• Acute myocardial infarction has been reported in clinical trials 2
• Elevated heart rate is a common side effect requiring monitoring 2
• Cardiac arrhythmia/tachycardia may occur; if symptomatic, monitoring and consideration of beta blockers may be necessary 2

Hypoglycemia Risk

• Ozempic carries very low intrinsic hypoglycemia risk when used alone due to its glucose-dependent mechanism of insulin secretion 2
• However, risk for low blood sugar increases significantly when combined with insulin or insulin secretagogues (sulfonylureas or glinides), requiring dose reduction of these medications 2, 1
• Signs and symptoms include dizziness, blurred vision, anxiety, sweating, slurred speech, confusion, shakiness, weakness, headache, and fast heartbeat 1

Diabetic Retinopathy Complications

• Changes in vision may occur during treatment with Ozempic 1
• Patients with a history of diabetic retinopathy should be monitored closely for progression when using semaglutide 2
• Due to its potent glucose-lowering effect, patients at risk for deterioration of existing diabetic retinopathy should be carefully monitored, particularly if also treated with insulin 4

Thyroid C-Cell Tumor Risk

• Ozempic carries an FDA Black Box Warning regarding the risk of thyroid C-cell tumors based on rodent studies 2
• Absolute contraindication in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2, 3, 1

Other Notable Side Effects

• Injection site reactions occur with subcutaneous administration 2
• Insomnia has been documented as a side effect, with risk similar to other GLP-1 receptor agonists 3
• Suicidal ideation has been reported in clinical trials 2, 3
• Severe constipation, small bowel obstruction, or ileus progression may occur 2

Gastroparesis Considerations

• Do not use Ozempic in patients with clinically meaningful gastroparesis, as semaglutide delays gastric emptying and may worsen symptoms 2
• Patients with severe gastroparesis may experience worsened symptoms due to delayed gastric emptying 2

Drug Interactions and Special Precautions

• Ozempic affects absorption of concomitantly administered oral medications due to delayed gastric emptying, particularly those with narrow therapeutic index like warfarin 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 2
• Do not mix insulin and Ozempic together in the same injection 1

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma or MEN 2 2, 1
• Pregnancy or breastfeeding 2

Monitoring Recommendations

• Regular monitoring of renal function, gastrointestinal symptoms, signs of pancreatitis, and gallbladder disease is advised 2
• Monitor for sleep disturbances, especially during initial titration phase 3
• Check blood sugar as directed by healthcare provider 1
• Monitor for signs of dehydration, particularly with severe GI side effects 2, 1

Critical Management Point: If more than 5 days have passed since a missed dose, skip it and resume on the regularly scheduled day; if 3 or more consecutive doses are missed, restart the titration schedule 2, 1