What is the biggest side effect of Ozempic (semaglutide)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: August 19, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

The Biggest Side Effect of Ozempic (Semaglutide)

Gastrointestinal side effects, particularly nausea, are the most common and significant side effects of Ozempic (semaglutide). 1, 2

Primary Gastrointestinal Side Effects

Semaglutide causes several gastrointestinal adverse effects, with nausea being the most prominent, followed by:

  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Constipation

These side effects occur due to semaglutide's mechanism of action, which delays gastric emptying 1. According to the FDA label, these gastrointestinal effects are reported as the most common adverse reactions, occurring in ≥5% of patients treated with Ozempic 2.

Management of Gastrointestinal Side Effects

To minimize these gastrointestinal effects, the following strategies are recommended:

  • Gradual dose titration: Start with the lowest dose and increase slowly 1
  • Dietary modifications:
    • Reduce meal size
    • Avoid high-fat foods
    • Limit alcohol and carbonated beverages 1
  • Timing of administration: Maintain consistency in administration timing 3

Other Serious Side Effects

While gastrointestinal effects are most common, several other serious adverse effects require monitoring:

Pancreatitis

  • Stop using Ozempic immediately and seek medical attention if severe abdominal pain occurs 2
  • Pancreatitis has been reported in clinical trials, though causality hasn't been definitively established 1

Gallbladder Disorders

  • Semaglutide increases the risk of cholelithiasis (gallstones) and cholecystitis 1
  • These are typically less common than the gastrointestinal effects but represent significant concerns

Hypoglycemia

  • Risk increases when combined with insulin or insulin secretagogues 2
  • Requires dose adjustment of these medications when used with semaglutide

Rare but Serious Concerns

  • Acute kidney injury, particularly in patients with pre-existing kidney problems 2
  • Diabetic retinopathy complications, especially in patients with pre-existing retinopathy 1, 4
  • Serious allergic reactions requiring immediate medical attention 2

Contraindications

Semaglutide is contraindicated in:

  • Patients with personal or family history of medullary thyroid carcinoma
  • Patients with Multiple Endocrine Neoplasia syndrome type 2 1, 3
  • Patients with gastroparesis, as it may worsen symptoms 3, 5

Practical Considerations

  • The FDA reports that nausea, vomiting, diarrhea, abdominal pain, and constipation are the most common side effects (reported in ≥5% of patients) 2
  • Gastrointestinal side effects are typically most pronounced during the initial weeks of treatment and often diminish over time 4
  • Patients should be monitored closely during dose escalation periods when side effects are most likely to occur
  • Proper education about administration is crucial to avoid dosing errors that can exacerbate side effects 6

While Ozempic offers significant benefits for weight management and glycemic control, the predominant gastrointestinal side effects, particularly nausea, represent the biggest challenge for most patients using this medication.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Type 2 Diabetes Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Safety of Semaglutide.

Frontiers in endocrinology, 2021

Research

Administration errors of compounded semaglutide reported to a poison control center-Case series.

Journal of the American Pharmacists Association : JAPhA, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.