Should patients take a Proton Pump Inhibitor (PPI) while on Ozempic (semaglutide)?

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Last updated: May 13, 2025View editorial policy

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From the Guidelines

Patients on Ozempic (semaglutide) do not necessarily require a proton pump inhibitor (PPI) unless they have a pre-existing condition that necessitates PPI therapy, such as gastroesophageal reflux disease (GERD), peptic ulcer disease, or Barrett's esophagus. Most patients on Ozempic do not need to routinely take PPIs like omeprazole, pantoprazole, or esomeprazole 1. However, some patients may experience increased acid reflux or heartburn when starting Ozempic, as it can slow gastric emptying. In these cases, a short course of PPIs might be considered to manage these symptoms.

The decision to use a PPI should be individualized based on the patient's specific symptoms and medical history, taking into account the latest guidelines on PPI use and de-prescribing 1. According to the AGA clinical practice update on de-prescribing of proton pump inhibitors, patients with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture should generally not be considered for PPI discontinuation 1.

Key considerations for PPI use in patients on Ozempic include:

  • Patients with complicated gastroesophageal reflux disease should generally not be considered for PPI discontinuation 1
  • Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing 1
  • PPI users should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy before de-prescribing 1
  • Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing 1

Ultimately, the decision to use a PPI in patients on Ozempic should be based on a thorough evaluation of the patient's individual needs and medical history, with consideration of the potential benefits and risks of PPI therapy 1.

From the Research

Proton Pump Inhibitors (PPIs) and Ozempic

  • There is no direct evidence in the provided studies regarding the use of PPIs with Ozempic.
  • However, the studies discuss the efficacy of PPIs in treating gastroesophageal reflux disease (GERD) and other acid-related disorders 2, 3, 4, 5, 6.
  • PPIs are commonly used to reduce stomach acid production and are often prescribed for patients with GERD or other conditions that cause acid reflux.
  • Ozempic (semaglutide) is a medication used to treat type 2 diabetes, but it can also cause gastrointestinal side effects such as nausea, vomiting, and diarrhea.

PPIs and GERD Treatment

  • The studies suggest that PPIs are effective in treating GERD, with higher doses leading to improved esophageal healing and relief of symptoms 2, 4, 6.
  • A systematic review and meta-analysis found that increasing PPI doses led to improved GERD outcomes, but the impact of twice-daily dosing was inconsistent across different PPI strength comparisons 6.
  • Another study found that fluoxetine was superior to omeprazole in improving symptoms of patients with heartburn and normal endoscopy who failed once-daily PPIs 5.

Considerations for Patients on Ozempic

  • While there is no direct evidence on the use of PPIs with Ozempic, patients on Ozempic who experience gastrointestinal side effects such as acid reflux may benefit from PPI treatment.
  • However, the decision to prescribe PPIs should be made on a case-by-case basis, taking into account the individual patient's medical history and current medications.
  • Further studies are needed to determine the safety and efficacy of using PPIs in combination with Ozempic.

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.

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