What are the side effects of Ozempic (semaglutide)?

Side Effects of Ozempic (Semaglutide)

Ozempic most commonly causes gastrointestinal side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation, which occur in the majority of patients but are typically dose-dependent and transient. 1

Common Gastrointestinal Side Effects

The FDA-approved labeling identifies the following as the most frequent adverse reactions (occurring in ≥5% of patients):

• Nausea, vomiting, diarrhea, abdominal pain, and constipation are the predominant side effects 1
• These symptoms are typically dose-dependent and more pronounced during initial treatment or dose escalation 2
• Slow dose titration (starting at 0.25 mg weekly for 4 weeks, then 0.5 mg, then 1 mg if needed) minimizes these gastrointestinal effects 2
• Esophageal reflux and flatulence also commonly occur due to delayed gastric emptying 2, 3

Management strategies include: reducing meal size for nausea/vomiting, limiting alcohol and carbonated drinks for reflux, and avoiding high-fat diets for constipation 2

Serious Adverse Events Requiring Monitoring

Clinical trials demonstrate a 38% higher risk of serious adverse events with semaglutide compared to placebo 2, 3, including:

Pancreatitis

• Acute pancreatitis has been reported in clinical trials, though causality remains unestablished 2, 3
• Stop Ozempic immediately if severe abdominal pain occurs that will not go away, with or without vomiting 1
• Use with caution in patients with prior pancreatitis history 2

Gallbladder Disease

• Increased risk of cholelithiasis (gallstones) and cholecystitis requiring regular monitoring 2, 3
• Monitor for signs of gallbladder disease periodically 2

Acute Kidney Injury

• Risk of acute kidney injury from dehydration, particularly in patients with pre-existing kidney disease 2, 3
• Diarrhea, nausea, and vomiting may cause fluid loss leading to kidney problems worsening 1
• Monitor renal function closely when initiating or escalating doses, especially with severe gastrointestinal symptoms 2
• Ensuring adequate fluid intake is crucial to prevent dehydration-related kidney injury 2

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, consider beta blockers 2

Absolute Contraindications

Ozempic carries an FDA Black Box Warning and is absolutely contraindicated in:

• Personal or family history of medullary thyroid carcinoma (MTC) 2, 3
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2, 3
• Pregnancy or breastfeeding 2

Hypoglycemia Risk

• Semaglutide carries very low intrinsic hypoglycemia risk due to glucose-dependent insulin secretion 2
• Increased hypoglycemia risk occurs only when combined with insulin, sulfonylureas, or glinides 2, 1
• Reduce doses of insulin or sulfonylureas when initiating Ozempic to prevent hypoglycemia 2

Signs of hypoglycemia include: dizziness, blurred vision, anxiety, sweating, slurred speech, confusion, shakiness, weakness, headache, and fast heartbeat 1

Special Populations and Precautions

Gastroparesis

• Do not use in patients with clinically meaningful gastroparesis 2
• Semaglutide delays gastric emptying and may worsen symptoms 2, 4

Diabetic Retinopathy

• Monitor patients with history of diabetic retinopathy closely for progression 2
• Tell your healthcare provider if you have changes in vision during treatment 1

Renal Impairment

• Can be used with caution in severe renal impairment or end-stage renal disease (no dose adjustment needed) 2
• Requires careful monitoring for gastrointestinal side effects that could lead to dehydration 2

Drug Interactions

• Delayed gastric emptying affects absorption of concomitantly administered oral medications 2
• For oral hormonal contraceptive users: switch to non-oral contraception or add barrier method for 4 weeks after initiation and each dose escalation 2
• Particular concern with narrow therapeutic index drugs like warfarin 2

Other Notable Side Effects

• Injection site reactions with subcutaneous administration 2
• Insomnia has been documented in clinical guidelines 3
• Suicidal ideation has been reported in clinical trials 2, 3
• Severe constipation, small bowel obstruction, or ileus progression may occur 2

Monitoring Recommendations

Assess efficacy and safety at least monthly for the first 3 months, then at least quarterly thereafter 2, including:

• Renal function monitoring, especially with severe gastrointestinal symptoms 2
• Signs of pancreatitis (severe abdominal pain) 2
• Gallbladder disease symptoms 2
• Blood glucose levels and hemoglobin A1C 1
• Heart rate monitoring 2
• Sleep disturbances, especially during initial titration 3

Dose Adjustment for Missed Doses

• If you miss a dose, take it as soon as possible within 5 days 1
• If more than 5 days have passed, skip the missed dose and resume regular schedule 1
• If 2 consecutive doses are missed and previously tolerated well, resume at same dose 2
• If 3 or more consecutive doses are missed, restart the titration schedule 2

Critical Safety Considerations

Do not share your Ozempic pen with other people, even if the needle has been changed, as this may transmit serious infections 1

If a patient tolerates a submaximal dose well and achieves adequate response, continuing that dose long-term is acceptable rather than escalating 2