Gastroesophageal reflux disease is a clinical syndrome characterized by heartburn and acid reflux caused by the reflux of stomach and duodenal contents into the esophagus? Gastric juice flows back into the lumen of the esophagus, and since the esophagus lacks a protective mucosal layer, gastric acid corrodes and damages the esophageal mucosa causing erosion and ulceration. Most treatments for GERD are based on the inhibition of gastrointestinal secretion production, so they are mostly treated with H2 receptor blockers or proton pump inhibitors. Proton pump inhibitors are the most widely used drugs and have the ability to provide more effective long-term relief and promote healing of damaged esophageal mucosa. However, because proton pump inhibitors reduce gastric acid secretion, they inhibit the hydrolysis of gastric contents and increase gastrin secretion, resulting in a significant decrease in the amount of fluid secreted into the stomach, thus delaying gastric emptying to some extent (15-40%). Delayed gastric emptying can lead to a range of digestive disorders, including increased GERD symptoms, peptic ulcers, and functional dyspepsia. Mosapride is a selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist that promotes the release of acetylcholine and stimulates the gastrointestinal tract to exert a prokinetic effect, thereby improving gastrointestinal symptoms in patients with functional dyspepsia without affecting the secretion of gastric acid. LimHC and his team at Gangnam Severance Hospital, Yonsei University School of Medicine, Seoul, Korea, conducted a prospective – randomized – double-blind – placebo-controlled clinical trial to evaluate whether mosapride can prevent proton pump-induced delayed gastric emptying. The trial included 30 patients with a diagnosis of GERD and normal gastric emptying. The study subjects were randomized into 2 groups. One group was the proton pump monotherapy group, which was given pantoprazole combined with placebo. The other group was given pantoprazole combined with mosapride and both groups were treated with the drug for 8 weeks. Gastric emptying scans were performed before and after treatment, and gastroesophageal reflux symptoms and dyspeptic symptoms were scored using a questionnaire. Gastrin and cholecystokinin are important components of gastrointestinal endocrine hormones that are associated with physiological functions such as gastric acid secretion, gastric emptying, growth of gastric mucosa, and the dynamics of upper gastrointestinal peristalsis. In order to assess the changes in the gastrointestinal endocrine hormone profile induced by proton pump inhibitors that can affect gastric acid secretion and gastric motility, fasting plasma gastrin and cholecystokinin levels were monitored before and at week 8 of drug administration. Gastric half-emptying time (the time required to halve the postprandial increase in gastric sinus volume) was significantly increased in the proton pump inhibitor monotherapy group, whereas there was no significant change in gastric half-emptying time in patients in the proton pump inhibitor combination with mosapride, with a statistically significant difference between the two groups (P=0.023). Similarly serum gastrin levels increased significantly in patients in the proton pump inhibitor monotherapy group, while there was no significant change in patients in the combination group, with the same statistically significant difference between the two groups (P=0.028). No significant changes in cholecystokinin levels were observed in either group after treatment. Gastroesophageal reflux symptoms improved in both the proton pump inhibitor monotherapy group and the proton pump inhibitor combined with mosapride, while postprandial bloating and nausea were significantly reduced in the proton pump inhibitor combined with mosapride group. These trials showed that mosapride was effective in preventing delayed gastric emptying and increased gastrin levels caused by the use of proton pump inhibitors. However, there was no outstanding advantage of the combination in terms of clinical symptom improvement. The data from this trial confirm that the combined use of mosapride and proton pump inhibitors in the treatment of GERD is effective in alleviating the adverse effects caused by proton pump inhibitor application that persist after long-term use or discontinuation. However, there are many limitations in the article, such as small sample size and differences in the study population itself in terms of gender due to follow-up of patients out of the pilot study, etc. Therefore, a larger clinical study is needed to better understand the effects of mosapride in preventing delayed gastric emptying and gastrin hypersecretion caused by proton pump inhibitors, as well as the improvement of patients’ complaints.