Comparing the efficacy of different proton pump inhibitor dosing regimens for the treatment of gastroesophageal reflux disease: a systematic review and meta-analysis

Several proton pump inhibitor (PPI) dosing regimens that vary by strength and frequency (once [Qday] or twice [BID] daily) are available to treat gastroesophageal reflux disease (GERD). We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the impact of various PPI regimens on esophageal healing and GERD and heartburn symptoms. To identify relevant studies, we searched EMBASE and PubMed in January 2023, which yielded 1381 records. Eligible RCTs included those that enrolled adults diagnosed with GERD and compared different dosing regimens within the same PPI. The outcomes were esophageal healing and resolution of GERD and heartburn symptoms within 12 weeks (i.e. short-term) and > 12 weeks (i.e. long-term). Meta-analysis pooling of the odds ratios with 95% confidence intervals were estimated using the random-effects inverse-variance model. Overall, a total of 38 RCTs across 20 countries (N = 15,540 patients, mean age 50 years, 55% male) were included. Most PPI trials compared half standard dose Qday versus standard dose Qday or standard dose Qday versus double standard dose Qday. In general, when considering daily dosing, higher PPI strength significantly improved esophageal healing and relief of GERD symptoms both in the short- and long-term. Fewer trials compared Qday versus BID dosing; the impact of BID dosing on outcomes was inconsistent across the different PPI strength comparisons. In conclusion, this meta-analysis revealed that increasing PPI Qday dosages led to improved GERD outcomes. However, few studies compared Qday to BID dosing; as twice daily PPI usage is common in clinical practice, further studies are warranted to determine whether such dosing improves clinical outcomes.