J Neurogastroenterol Motil.  2021 Apr;27(2):165-175. 10.5056/jnm20161.

A Systematic Review and Meta-analysis of Randomized Control Trials: Combination Treatment With Proton Pump Inhibitor Plus Prokinetic for Gastroesophageal Reflux Disease

  • 1Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 2Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul, Korea


Prokinetics can be used for treating patients with gastroesophageal reflux disease (GERD), who exhibit suboptimal response to proton pump inhibitor (PPI) treatment. We conducted a systematic review to assess the potential benefits of combination treatment with PPI plus prokinetics in GERD.
We searched PubMed, the Cochrane Library, and EMBASE for publications regarding randomized controlled trials comparing combination treatment of PPI plus prokinetics to PPI monotherapy with respect to global symptom improvement in GERD (until February 2020). The primary outcome was an absence or global symptom improvement in GERD. Adverse events and quality of life (QoL) scores were evaluated as secondary outcomes using a random effects model. Quality of evidence was rated using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
This meta-analysis included 16 studies involving 1446 participants (719 in the PPI plus prokinetics group and 727 in the PPI monotherapy group). The PPI plus prokinetics treatment resulted in a significant reduction in global symptoms of GERD regardless of the prokinetic type, refractoriness, and ethnicity. Additionally, treatment with PPI plus prokinetics for at least 4 weeks was found to be more beneficial than PPI monotherapy with respect to global symptom improvement. However, the QoL scores were not improved with PPI plus prokinetics treatment. Adverse events observed in response to PPI plus prokinetics treatment did not differ from those observed with PPI monotherapy.
Combination of prokinetics with PPI treatment is more effective than PPI alone in GERD patients. Further high-quality trials with large sample sizes are needed to verify the effects based on prokinetic type.


Gastroesophageal reflux; Gastrointestinal agents; Proton pump inhibitors
Full Text Links
  • JNM
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2021 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr