Improvement of meal‐related symptoms and epigastric pain in patients with functional dyspepsia treated with acotiamide was associated with acylated ghrelin levels in Japan

Background The aim of this study is to clarify whether acotiamide and rabeprazole combination therapy can improve clinical symptoms, gastric emptying, and satisfaction with treatment in functional dyspepsia (FD) patients more effectively than acotiamide or rabeprazole monotherapy alone. We also aimed to determine whether acotiamide affects these changes via its effect on gastric emptying and appetite‐related hormones such as ghrelin. Methods We used Rome III criteria to evaluate upper abdominal symptoms and anxiety by the State‐Trait Anxiety Inventory (STAI). Gastric motility was evaluated by the 13C‐acetate breath test. Eighty‐one FD patients were treated with acotiamide (300 mg/day) (n = 35), acotiamide (300 mg/day) and rabeprazole (10 mg/day) (n = 28), or rabeprazole (10 mg/day) (n = 18) for a period of 4 weeks and followed after 4 weeks of no treatment. Adenocorticotropic hormone (ACTH), cortisol, leptin and ghrelin levels were measured in all FD patients. Key Results Acotiamide and rabeprazole combination therapy significantly improved postprandial distress syndrome (PDS)‐like symptoms (p = 0.018, p = 0.04 and p = 0.041, respectively) and epigastric pain (p = 0.024) as wells as STAI‐state scores (p = 0.04) compared to rabeprazole monotherapy. Both acotiamide monotherapy, and acotiamide taken in combination with rabeprazole, significantly (p = 0.001 and p = 0.02, respectively) improved satisfaction with treatment, compared to rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy had no significant effect on ACTH and cortisol levels in FD patients. Of interest, acotiamide monotherapy, and acotiamide and rabeprazole combination therapy, significantly (p < 0.0001 and p = 0.018, respectively) increased acylated ghrelin/total ghrelin ratios and significantly (p = 0.04) improved impaired gastric emptying compared to rabeprazole monotherapy. Conclusions & Inferences Further studies are warranted to clarify how acotiamide treatment improves clinical symptoms in FD patients. We aimed to clarify whether acotiamide and rabeprazole combination therapy significantly improves clinical symptoms and satisfaction with treatment via its effect on gastric emptying and appetite‐related hormones such as ghrelin, compared to acotiamide or rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy significantly improved PDS‐like symptoms and epigastric pain and STAI‐state scores compared to rabeprazole monotherapy. Acotiamide monotherapy, and a